MUSCULAR DYSTROPHY ASSOCIATION - ROMANIA

DONATE FOR THE ROMANIAN PEOPLE WITH MUSCULAR DYSTROPHY

2010-04-17T03:31:00.000-07:00

DONATE FOR US! WE WILL HELP PEOPLE WITH MUSCULAR DYSTROPHY IN ROMANIA, poor people with an allowance of 100 euro per month or less , that cannot afford even a decent life and treatments. Through our programs we will offer them a solution to be on their own. If only we had some money to start the courses of french and english language, arts and crafts, PC, accountancy and secretarial course, web promoter and drawing/peinture course.

DONATE FOR US! 35.000 PEOPLE WITH MUSCULAR DYSTROPHY WOULD FULFILL THEIR DREAMS FOR A PROFESIONAL CAREER FOR AN ACTIVE AND INDEPENDENT LIFE.

ASOCIATIA DISTROFICILOR MUSCULAR din ROMANIA
COD FISCAL: 8896012

cod IBAN lei: RO94RZBR0000060012378811
RAIFFEISEN BANK

str. Bailor,Nr. 197, Loc. Vâlcele, jud. Covasna,

Tel.: +4 0720.04.98.19
e-mail: admrvalcele06@yahoo.com
asociatiadistroficilormuscular@gmail.com

MARIA TEODORESCU, preşedinte
Tel. +4 0720.04.98.19
e-mail: maria_sirghi@yahoo.com

VOLUNTEER MEMBERS
DANIELA TONTSCH
e-mail: danielatontsch@yahoo.com
CATALINA-OANA DRUTA
e-mail: druta.oanacatalina@yahoo.com

MDA ROMANIA signed a partnership with the local hall

2010-04-17T03:27:00.000-07:00

In December 2009, ADMR local Hall filed a letter of intent to terminate a partnership.

Partnership with City Valcele is a precondition for EU Funding the infrastructure grants.

Driven in partnership with city hall as recommended by the Council of Europe Committee of Ministers signed.

Today January 27, 2010 president of ADMR, Maria Teodorescu met with Mr. Mayor Dumitru Marinescu, both of which signed the Partnership gleaned:

ADMR is the developer" may remain useful to society! "Project for people with muscular dystrophy, to establish a training center and physical recovery.

ADMR aims to encourage educational and professional information among people with disabilities, but that activating and recovery center.

The main objectives of the project:

ADMR The project is committed to provide free assistance and advice to City Hall in the process of this agreement.

Assistance and advice will be given to the project:

• project implementation by financing non-reimbursable European funds;

• preparation and information campaign

• preparing and conducting training seminars to interested parties and local training team members.

• ensuring local team with equipment and consumables during project implementation;

• develop model contracts and making them available to the local council secretary.

The project, jointly with the Hall:

• to develop and use assessment methods to one implementation of the project;

• will carry out project development planning;

• assist owners and local team in implementing and recording project financing agreements;

The project will support the following types of expenses:

The secondary objectives of the project are:

-Increasing number of people with motor disabilities in normal schools and the involvement of this purpose.

-Improving the quality and perception of life for facilitating professional activities and for dealing in motor disabled persons are disadvantaged, appealing to the authorities responsible.

ROMANIAN PEOPLE WITH MUSCULAR DYSTROPHY NEED OUR SUPPORT

2010-04-17T02:44:00.000-07:00

Muscular Distroficilor Association of Romania (MDA ROMANIA), based in Valcele needs help to raise funds for carrying out its business specific opportunity. The association aims primarily to promote the interests of its members through social integration of those suffering from muscular dystrophy.

MDA ROMANIA President, Maria Teodorescu, said that the problems of the organization is not only to revolved around the lack of money for the association programs but also there's a lack of money to create a suitable space for the disabled people especially those the suffer from muscular dystrophy disease.

Currently, the MDA ROMANIA activity takes place in the virtual world, as the bulding of the association after this cold winter is unusable. Association calls for investment in building rehabilitation, and equipment for heating fuel (LPG) and specific equipment maintenance distroficilor gymnastics. ( but this takes more time so we need everybody's support to create a better place for this disabled comunity in Romania )

The only income, Membership fees, 3 euros or 4 dollars

President MDA ROMANIA says that currently does not really have any financial situation, its only income comes from the membership fees - 3 euros or 4 dollars per person per year.

Beyond the urgent needs related to the heating and Rehabilitation of the Association there is a need for an entire modernization, by setting a recovery room, a leisure club with educational games for children and young people, a computer room and a mini library, which will serve including those admitted to the hospital Horia Radu in Valcele ( the only existent recovery center for muscular dystrophy people)

"If we talk about modernization, its headquarters said that this joint project needs to be realized with around 80,000 euros. We thought of accessing European funds, because the building is right in legally, the property of the Association, we have been promised help from City Hall of Valcele and hopefully help of donations. We do not necessarily want money, we could use building materials or donations of all sorts of things needed. We need furniture for bedrooms - including some for the camps that we want to organize for our members, we need new equipment to exercise, bathroom and kitchen equipment also. "said MDA ROMANIA President.

Ignored by our society,
In this context, Maria Teodorescu wanted to launch an appeal to all those who want to help the Association, asking them to this target of 2% of tax.

"We appeal to your goodwill, support and kindness, instead we are offering a smile and the gratitude of those oppressed by fate and the company ignores us all. Romania is going through a very difficult period, it is difficult for each of us to survive financially, but who still have a job, may direct that 2% of income tax to our Association, because any kind of aid is appreciated.

For those who want to provide support and assistance MDA ROMANIA, identification of the Association is:
Contact
ASOCIATIA DISTROFICILOR MUSCULAR din ROMANIA
COD FISCAL: 8896012

cod IBAN lei: RO94RZBR0000060012378811
RAIFFEISEN BANK

str. Bailor,Nr. 197, Loc. Vâlcele, jud. Covasna,

Tel.: +4 0720.04.98.19
e-mail: admrvalcele06@yahoo.com
asociatiadistroficilormuscular@gmail.com

MARIA TEODORESCU, preşedinte
Tel. +4 0720.04.98.19
e-mail: maria_sirghi@yahoo.com

VOLUNTEER MEMBERS
DANIELA TONTSCH
e-mail: danielatontsch@yahoo.com
CATALINA-OANA DRUTA
e-mail: druta.oanacatalina@yahoo.com

We are looking for volunteers- MDA RO

2010-04-17T01:54:00.000-07:00

My name is Oana Catalina Druta and I'm a volunteer member of the Association Distroficilor Muscular managerial office in Romania with headquarters in place. Valcele, Covasna County will submit a petition on behalf of muscular dystrophy patients to give us a free consultation to access grant funds on infrastructure: rehabilitation of the building where we want to activate and currently can not because they are humane. Initially we want to bring in front a creative workshop where disabled people will assert their talent through exhibitions of all creations. If you respond favorably to this request, 1200 people suffering from this disease will learn to smile. Our office is near the only hospital in the country to diagnose and monitor the muscular dystrophies. Imagine a form of escape when a person is in hospital. It is our important objective. The Association's activity is based on social model of disability, the fact that disability is the social consequence of disease and as such is society that must change to ensure full inclusion of persons with disabilities.

Like any other organization that must raise money to make themselves known in the community, to join the programs depend on sponsors, we have more work to be done. People need opportunities and to capitalize on the chances and those with special needs more, they need incentives, education, appreciation and respect.

On 12 th of March, 2010, ADMR expressed an opinion...

2010-04-17T01:36:00.000-07:00

During the National Conference of the Patients, MDA ROMANIA expressed its opinion according to the improvement of the medical services accorded to the dystrophics.

The body of delegates was made up of – Loloiu Iulian, Apreotesei Marian, Liteanu Zoica, Morosan Petru, Tontsch Peter Klaus, Tontsch Daniela. We thank them all.

We attach the discourse made by Druta Oana Catalina and Daniela Tontsch -

THE SITUATION OF THE PATIENTS WITH DISTROPHY

We greet and offer the organiser our congratulations according to this event as well as all the active participants in the improvement of the patients life from Romania.

In my discourse I directly refer to the distrophyc patients, who are born ill and that is why all the doctors from our country directed our steps towards the only hospital of this type which is to Valcele, Covasna county, led by doctor Radu Horia. His activity is made up of the developed neuro-muscle heredity which especially affects the child and the young adult. It was registered over 35000 cases of such affections.

To this moment, the Neuro-Muscle centre – DR . RADU HORIA – Hospital include 81 beds -60 beds for the adults and 21 for children.
A very serious problem of the distrophyc people is that they are refused to be in other hospitals where there are specialists for their therapy. As i mentioned before, there are 35000 of distrophycs and we know that 2916 would have the posibility to be hospitalzed for 30 days but from these persons 2835 people can not be hospitalized because there are not enough beds. It is known that this illness is characterized by the progressive deterioration of the muscles and invalidity. To all these the absence of the hospitals also contribute to the developing of this kind of affection.
In some kinds of distrophycal forms the miocard muscle is affected together with other organs and also these patients are refused to be hospitalized because this is the evolution of their illness and the doctors can not do anything for their remedy. We do not want to be misunderstood that we denigrate the medicine and their representatives, quite the contrary we ask their help whenever we need. I ca not help giving a personal experience- A few years ago I had a high fever, 38-39 degrees, I had an awful headache and sick. I called the ambulance and the doctor prescribed me anthibiotics. I took the treatment but my state was more and more worse. For 6 days I called the ambulance 6 times and by chance I met a trainee doctor who diagnosticated me corectly – acute appendicitis. She said the she had not wanted to leave without me because I immediately need hospitalization. After 15 minutes I was in the operate hall. I can not remember her name but I am alive because she accorded a serious attention to their studies and she knew to practice what she had learnt. I am very grateful to her and I am sure that she saved lives now on.

Coming back to the distrophy problems, we remind that a patient like this needs an accompanying permanently and where they are allowed to be hospitalized it is refused the permanently presence of the accompanying because there are enough medical staff to take care the patient. But it is not known that every patient has a different type of care . There is no calificated staff according to this type of illness and we do not pretend to be because we pay our accompanying who is calificated with the care of the persons with disabilities. We solicitate tolerance because we need a permanent accompanying during our hospitalized period. If these 2 needs are accepted there are solutions, too. It is inhumanely that an accompanying who is a member of the family to stay on a chair near the patient during his period in a hospital.

There are situations when the buildings, the rooms and the toilets from the hospital are not equipped with space of moving the wheelchairs, there are no ramps and elevators.

There is no curative treatment for the muscle distrofy, the existing medications and the therapy has the role of slowing down the evolution of the illness. The main medication is the therapy with vitamins but they are too expensive to use them quite often.

For that patient who is imobilized in a wheelchair, it is urgenly needed by the medical furniture such as a bathroom chair, the elevating of toilet and the tub chair. The nursing home does not pay us to buy all these things. The accompanying who raises up several times a day a person who is inert, he is at risk to become a patient, too.

The same problem is to buy an electric wheelchair because the nursing home has not enough money to do that. We admit that is too expensive but we solicitate to pay it by instalments. We informed about the facilities offered by other countries according to these acquisitions and we amaisingly descovered that these are offered by state and they are changed when they are made use of.

It is very important the existence of the centres with calificated staff for the care of the patients and we prove the great number of distrophics. There are many cases when they have no family or they have old parents who live in an asylum or maybe they do not have an accompanying. Fancy yourself such a life.

Imagine that you could not put on or eat by yourselves, to stay isolated in the house without seeing the sunrise or not to touch your ideals!

The highbrow compensates the severe, ireversible and progressive affection of the striate muscles.

We want to believe that these mentioned above were not known and we hope to be solutionated all these demands so that the distrophics can be useful in our society for their intellectuals capacities that are not affected by the terrible illness.

MDA ROMANIA celebrates 20 years of outliving

2010-04-17T01:31:00.000-07:00

We are very happy as we have a moral supporter in the journalist Horia Deliu, who is the person raises us our spirits when we feel that we break down in our survival to be heard....

ADMR – 20 years of survival

29th 0f March, 2010

Hopes, strains, trobles but we do not make out the success. -

It seems to be yesterday. Although it passed 20 years, I perfectly remember the beginnings. Well, this month it is 20 years since ADMR was founded with the centre to Valcele. Together with the president Stelian Schipor – who at the present is a spokesman and according to his will the function as a leader is officiated by Mrs Maria Teodorescu, we set out our tumultous history of this organisation – it came into being since Revolution as an objective neccesity as all the pacients being in the wheelchair to be integrated with proudy and respect in the new society witch was to be forged then by comparison with the communist period.

At the beginning there was a group formed by some generous patients as Maria Molnar, Ioana Toderascu as well as some medical staff from Radu Horia hospital, Valcele – the doctors Mihai Popescu, Iulian Ionescu. They registered the new association with the CountyTribunal from Covasna and obtained legality with the approval of Department of Health.

Our period was not too easy – said Mr Stelian Schipor with objectivity, acoording to the last years. The mentality of the major people has not changed yet even it was 20 years since Revolution. All the members involved in the association, for example – the doctor Adriana Ghisoiu, doctor Iulian Ionescu, the engineer Iulian Loloiu, Daniel Colcer, Florinel Sfartz, Grigore Lungu, Steluta Diaconu, Mihaela Diaconu, Mihaela Nicolescu, Gheorgh Bratu do their best as this asociation survive.
Along years we achieved different direct contacts with abroad, we developped programmes together, more branches came into being like those from Arad – president Mihai Fighir – and Iasi – president Gheorghe Fighir.

Looking back with.....objectivity -

We actively involved in the building of the elevator from the Hospital of neuromuscle pathology -DR. Radu Horia – which was one of our grievances, because we were carried upstairs by someone.
We also managed to purchase a building in Valcele resort where we have many activities during the warm season but it is damaged inside because of the cold during winter. Not to mention many endowments we have done like a motor transport and many others during all these years.

Last year, in August, during the Yearly General Meeting, we elected a new team, which has the responsibility of developing new programes for our good association working.

Publicy thanks

To review I would propose to the Directory Office that during summer to organise at Valcele a festive Day dedicated to this important event – 20 years of hopes, strains, troubles -
In conclusion, on behalf of my name and my colleagues I worked so many years, we express thanks to all those who were by us, who contributted to all the association achieved. We express thank you, dear friends. Happy annversary, ADMR!

A sad matter of facts

That is true, there were many hopes, strains, troubles and also misunderstandings between members of the association. They are discontented with us, the civile society, the central and local authorithies, because our involvement was too short, too formal.
I confess this matter because I know very well the situation of ADMR as well as its foundation, trying to reflect the truth, the troubles about these tried people. With the only difference that the maliciousness and the disgust of some citizens are too strong according the persons with disabilities.

So, the so-named -hope – which is always evoked by the guvernments, is not caught sight of yet, or it only glimmers for the persons with disabilities, too. And, even if, we, the healthy people, survived as we can, imagine yourselves permanently dependent on somebody, in a wheelchair, all your life, as it says – a full stomach does not know what hunger is – .

HORIA C. DELIU

Ullrich congenital muscular dystrophy

2010-02-10T15:15:00.000-08:00

What is Ullrich congenital muscular dystrophy?

The congenital muscular dystrophies are a group of conditions which share early presentation and a similar appearance of the muscle. Congenital means ‘from birth’ and in congenital muscular dystrophy the initial symptoms are present at birth or in the first few months. Congenital muscular dystrophies are a very heterogeneous group of conditions and in the last few years a lot of effort has gone into identifying the separate entities and in locating the genes responsible for a number of these forms.
Ullrich congenital muscular dystrophy (UCMD) is a form of congenital muscular dystrophy with specific features:
• children are often double jointed in their hands and feet but have some tightness in other joints such as elbows or hips
• they have rigidity (stiffness) of the spine
• children tend to develop respiratory problems, which result in frequent chest infections and might require ventilatory support at night
The genes responsible for Ullrich congenital muscular dystrophy have recently been identified and lie on chromosomes 21 and 2. These 3 genes are responsible for the production of the protein collagen VI.

Which are the first signs?

Babies with UCMD often have hypotonia (low muscle tone or floppiness), and may have reduced movements. Other common signs are hip dislocation and a stiff neck (torticollis) and contractures (tightness) in the hips, knees and elbows. Some of these babies may also have feeding problems, which improve after a few weeks or months.
Sometimes the first signs are only noted after a few months when babies are observed to have poor head control or have a delay in learning new skills such as sitting unaided, crawling or walking.

Is UCMD Inherited?

Yes. The pattern of inheritance is known as ‘autosomal recessive’. This means that both parents are carriers of the condition (although clinically unaffected) and they have risk of 25%, or 1 in 4, in each pregnancy of passing the condition on to their children. Occasionally a case may be ‘sporadic’ which means is a one-off with little risk of recurrence in other children. However, the risk of recurrence in the offspring of these sporadic cases can be significant. All families with UCMD should be referred for genetic counselling.

How is UCMD diagnosed?

The diagnosis of UCMD is usually suspected from the history and examination. The specific diagnosis however is generally made by looking at a piece of muscle or skin (muscle and skin biopsy).
Before doing a muscle biopsy (which involves taking out a small piece of muscle, usually from the thigh) a few other tests may be done. One of these tests is a blood test which measures the level of a muscle protein (creatine kinase or CK) that however is generally only mildly raised. Muscle ultrasound may also help to detect abnormalities in the muscle. The technique is very simple, similar to the ultrasound studies carried out in pregnancy and may provide further evidence of the involvement of the muscle.
These tests provide a broad indication that there is a muscle problem but cannot pin-point the precise diagnosis. Muscle biopsy can provide a precise diagnosis in two ways:
• When the muscle is studied under the microscope, it is possible to look for signs, which might indicate a muscle problem. In children with a muscular dystrophy the muscle fibres, instead of being evenly sized, show a great variation and some of these fibres are replacedby fat and fibrous tissue.
• It is also possible to look at the presence of collagen VI in the muscle under the microscope. There are specific ‘tags’ which can interact with collagen VI and detect whether collagen VI is normally present or reduced. A reduction in collagen VI in a patient with evocative clinical features strongly suggests the possibility of Ullrich congenital muscular dystrophy. As collagen VI is normally present both in muscle and skin, taking a small piece of skin (skin biopsy) can also help to confirm the diagnosis. In some cases it is easier to detect a reduction of collagen VI on skin cells than on muscle cells. Taking a piece of skin however cannot provide some of the information that one can achieve with a muscle biopsy and it is therefore important to have both muscle and skin biopsies to obtain all the information needed.
The illustration overleaf shows where collagen VI is produced in the muscle fibres. In the upper part of the illustration, a number of relevant extracellular proteins and their interactions are showed. Collagen VI interacts, among other proteins, with biglycan and eventually with dystrolgycan. Dystroglycan is in turn associated, intracellularly, with the protein dystrophin. Genetic tests looking for abnormalities in one of the 3 genes responsible for Ullrich congenital muscular dystrophy are now available and provide the ultimate diagnosis. These tests however are still only done on a research basis and are very time consuming. The results are often only available after many months.
Prenatal diagnosis is a promising development in the diagnosis of inherited conditions. It is based on the ability to detect the abnormality in the developing foetus. In families who have a child with Ullrich congenital muscular dystrophy who decide to have another baby it is possible to detect whether the baby has deficiency of collagen VI and/or the same gene defect early in pregnancy.

Is there a treatment or cure?

At the moment there is no cure for congenital muscular dystrophy, but there are ways, described below, of helping to alleviate the effects of the condition.

Can a child with UCMD learn to walk?

The severity of this condition varies greatly from person to person. Some children will walk but sometimes this can be delayed. Children who have successfully walked may lose the ability later on because as they grow taller and heavier, their muscles are unable to cope with a greater strain. Leg splints (callipers) are often used to assist the child to walk.
Other children never achieve the ability to walk independently but can only stand and walk with
leg splints.

What other physical effects might Ullrich CMD have on a child?

As the muscles are weak and mobility is limited, the child may be born with or develop ‘contractures’, this means that the muscle tendons tighten up and the child is unable to move the limbs or the joints as freely as a healthy child. Physiotherapy can help prevent this and a programme of exercises which may be carried out daily by parents at home should be worked out with a physiotherapist very soon after diagnosis.
Even a very young baby can be helped to maintain suppleness. Hips are commonly affected and if they are dislocated this may require treatment with a splint or, only very, rarely surgery.
Most of the children with Ullrich congenital muscular dystrophy also develop a curvature of the spine (scoliosis)
As collagen VI is also normally present in the skin, children may have a tendency for scars to heal slowly or become thickened and elevated (keloid formation).

Is UCMD progressive and is it life threatening?

In the first years the condition is fairly stable and the child usually appears to gain strength as he
or she gets older. Motor function remains relatively stable but when children reach puberty, might experience increasing difficulties, as muscles find it difficult to cope with the greater strain
of increased weight and height.
Children who have achieved independent walking often need some help at this age and long leg callipers are often provided to assist them to walk.
While motor function remains relatively stable or only slowly progressive, children often experience breathing problems at night because the muscles which assist breathing are affected. It is therefore very important to monitor this function on a regular basis by performing ‘sleep studies’. This test is very simple and consists in applying a small wrapping around one finger. The wrapping is connected to a small machine which records the level of oxygen throughout the night. Night time breathing problems may happen in children of any age and, when present, children feel tired, often have headaches on waking in the morning, may feel sleepy during the day and lose appetite and weight. Another problem can also be that of frequent chest infections. If these signs are present or if the level of oxygen recorded at night are not satisfactory, children can be helped by referring them to a respiratory physician who will provide a means of supporting breathing at night (ventilator). This usually requires a special facial or nasal mask attached to a small machine which pumps air in and out of the lungs. Another frequent problem after the first few years is failure to thrive and it is therefore also important to monitor weight and height to be sure that children with Ullrich congenital muscular dystrophy receive enough food and energy. In several cases feeding supplements are needed. Sometimes a small surgical procedure called gastrostomy can be performed to help the child to receive the appropriate level of feeding to maintain his or her weight.

What help is available?

Physiotherapy is one of the main forms of help. An initial physiotherapy assessment at the time of the diagnosis should be followed by an exercise programme and regular check-ups. The main aim of physiotherapy is to keep the muscles as active as possible and to prevent the formation of contractures (muscle tendon tightness causing restriction in the range of joint movement). Children are encouraged to remain as active as possible. Swimming is a particular good form of exercise.
Physiotherapy can also help provide orthoses, such as splints and long leg callipers and a wheel chair when necessary.
It is also important to provide a proper sitting and standing posture to prevent curvature of the spine (scoliosis). If a curvature occurs a spinal brace may help to prevent further deterioration of
the curvature. Surgical intervention (scoliosis surgery) might be needed in some cases.

Oculopharyngeal muscular dystrophy (OPMD)

2010-02-10T15:12:00.000-08:00

The term muscular dystrophy is used to cover a wide range of conditions which have in common progressive muscle weakness due to an inherited genetic defect (mutation). There is huge variation in severity between the different conditions. Some present in very early childhood and progress to severe disability, whereas others can be extremely mild and not problematic even in old age. Each type relates to a specific genetic abnormality and if more than one family member is affected they each have the same type of muscular dystrophy. It has been recognised for many years that some patients with muscle disease have particular problems with the muscles around the eyes, although other parts of the body can also be involved. Whilst research is continuing, it appears that most of these patients have either oculopharyngeal muscular dystrophy (OPMD), the subject of this factsheet, or mitochondrial chronic progressive external ophthalmoplegia (CPEO). Often, when patients first present, it may not be clear whether the patient has OPMD or CPEO but specific investigations can differentiate between the two. The medical terms relating to these conditions may cause the lay person some confusion. They include: ptosis, external ophthalmoplegia, diplopia and dysphagia. Ptosis - this describes drooping of the eyelids due to weakness of the muscle that normally lifts up the eyelid. External ophthalmoplegia - this means weakness and restriction of muscle movement around the eye (external to the eye). It shows as slowness and incomplete range of movement of the eyes, and includes the eyelid muscle weakness that causes ptosis. These problems typically progress very slowly, hence the term 'chronic progressive external ophthalmoplegia'. Diplopia - this simply means double vision and occurs when the eye muscles on each side arenot affected equally, so that the eyes point in slightly different directions.
Dysphagia - this means difficulty in swallowing. When mild, it may simply be a feeling of food sticking in the throat, but patients with severe dysphagia may not be able to swallow at all and can even choke on their own saliva.

Symptoms and signs

Although the abnormal gene causing OPMD is present from birth, patients do not usually develop symptoms until the fifth or sixth decade of life. The first sign of the disorder is usually ptosis, but occasionally it is dysphagia. Very slowly, over many years, these problems progress. There is progressive restriction of eye movements and in rare cases this can lead to diplopia. The increasing ptosis may lead to the eyelid covering the pupil and impairing vision, and in an effort to compensate for this the forehead muscle becomes overactive, trying to help to lift up the eyelids, giving a frowning appearance, and the patient adopts a rather characteristic posture with the head tilted backwards. Dysphagia, which is initially mainly for solid and dry foods, progresses slowly and eventually
even swallowing fluids, including saliva, may become a problem. If dysphagia is severe there is a danger of aspiration (food, drink or saliva "going down the wrong way" - into the chest rather than stomach) which greatly increases the risk of a chest infection. After many years the patient may become aware of limb weakness, first around the shoulders and later around the hips. This is usually relatively mild but can occasionally be severe and disabling, many years after the first onset of symptoms. Facial weakness may develop, and be commented upon by the specialist, but rarely causes any particular problems. Life expectancy is little, if at all, altered.

Management

There is no specific treatment for OPMD, but much can be done to help the main symptoms of ptosis and dysphagia. Glasses can be fitted with fine metal bars (ptosis props) that lift up the drooping eyelids. If these are unacceptable, and if the ptosis is severe, surgical elevation of the eyelids can be very successful – several procedures are possible and should be tailored to the individual patient.
Mild dysphagia can be helped by suitable attention to the consistency of the diet (with a dietician's advice) and by exercises taught by a speech therapist. In more severe cases, a relatively minor operation called cricopharyngeal myotomy, which cuts one of the throat muscles
internally, can be valuable. Another approach that is sometimes helpful is to inflate a balloon to dilate the gullet. But as for all surgical procedures there are potential hazards and the final choice of treatment depends upon many individual factors. Recently there have been a few reports of the use of botulinum toxin injections; rather than cut or stretch a muscle, the toxin relaxes the muscle and that can aid swallowing. However, further studies are needed to see whether this will prove to be a useful long-term treatment. If the dysphagia is preventing adequate nutrition or there is a risk of aspiration pneumonia, then alternative methods of feeding can be used. The most acceptable, in the long term, is gastrostomy. A minor operation is used to pass a tube through the front of the abdomen directly into the stomach. Patients and their relatives find this easy to manage at home. If the normal diet is compromised, then a dietitian can offer advice with respect to supplements which can help to maintain adequate nutrition.
Physiotherapy may be useful to help patients cope with limb weakness, although this is usually mild, and to reduce the risk of chest problems.

How is OPMD inherited?

In almost all cases the condition is inherited as an autosomal dominant disorder which means that each child of an affected individual has a 50% risk of inheriting the same condition. It is now possible, through a blood test, to determine whether somebody has inherited the abnormal gene (called PABPN1) but that is not always terribly helpful. Even if somebody has inherited the abnormal gene, it is impossible to predict when, if ever, they will develop symptoms. Such testing should only be performed after detailed discussion with a suitably experienced neurologist or genetic counsellor.

Diagnosis

The diagnosis can be confirmed by a blood test that identifies the underlying genetic abnormality. Electrical tests (EMG) and muscle biopsy are now rarely necessary.

Is there any research being conducted into OPMD?

The genetic fault that causes OPMD was identified in 1998. Although this was a very important discovery, which has given us a simple diagnostic test, it is likely to be some considerable time before the research allows us to identify a specific treatment for this condition. In the meantime, there is a great deal of research trying to identify how the genetic fault causes the physical problem. Since 1998 over 100 research papers on OPMD have been published. Whilst none of these have yet led to a major change in management, they should be regarded as the building blocks for progress in the future.

Mitochondrial chronic external ophthalmoplegia (CPEO)

As mentioned above, this condition can be confused with OPMD. It is often sporadic (i.e. occurs in an individual with no family history of a similar condition) but occasionally is inherited so that there is a history of similarly affected relatives.
In CPEO the restriction of eye movements tends to be much more severe than in OPMD, but diplopia is still uncommon. As in OPMD, ptosis can be marked. Dysphagia is less common in CPEO than OPMD. Limb muscle weakness can be similar to that in OPMD, but may be more severe, and associated with exercise-intolerance.
Mitochondrial disorders can also affect other organs giving rise to deafness, diabetes, heart problems, and brain problems including epilepsy and dementia.
Other factsheets that may be useful
• Gastrostomy
• Mitochondrial myopathy (for more information on CPEO)

Nemaline (rod) myopathies

2010-02-10T15:02:00.000-08:00

Nemaline, or rod, myopathies are a group of conditions which fall under the umbrella of congenital myopathies. They are characterised by rod-like structures in the muscle cells, and clinical features such as muscle weakness, breathing problems, and feeding problems. There are 6 sub-groups which are defined according to age of onset and severity. Around 1 in 50,000 individuals are estimated to be affected, and these include both males and females. There is currently no effective treatment or cure to halt the progression, but management of the condition is very important and includes physiotherapy, and where necessary the use of ventilation and/or a feeding tube.

What is nemaline myopathy?

Nemaline myopathies, or rod body myopathies, are a group of conditions which fall under the category of congenital myopathies. There are a number of different types of rod myopathies and they affect both males and females. In the majority of cases (90%) the condition becomes apparent at birth or early childhood, although in very rare cases, it does not become apparent until adulthood. Rod myopathies are estimated to affect 1 in 50,000 individuals.

What causes it?

In the majority of cases, a rod myopathy is inherited, although there are sometimes sporadic cases where there are no other family members affected. There have been mutations identified in 5 different genes, which cause a rod myopathies. The protein products of all of these genes are involved in muscle tone and contraction.
ACTA1 - This gene produces a protein called α- actin. Mutations in this gene account for around 15-25% of cases. Errors in this gene are inherited in an autosomal dominant or autosomal recessive pattern.
NEM2 - The product of this gene is a protein called nebulin. It is thought that mutations in this gene are a common cause of nemaline myopathy but definite statistics are unavailable. Mutations in this gene are inherited in an autosomal recessive pattern.
TPM3 - The product of this gene is a protein called α- Tropomyosin 3. Mutations in this gene account for only 2-3% of affected individuals, and are inherited in an autosomal dominant or autosomal recessive pattern.
TPM2 - This gene encodes a protein called β-Tropomyosin. Only very few individuals have been identified with errors in this gene. Inheritance is in a autosomal dominant pattern. TNNT1 - This gene produces a protein called Troponin 1. Errors in this gene have only been identified in a population of Old Order Amish individuals. Inheritance is in an autosomal recessive pattern.

What are the common features?

There are six sub-groups of nemaline myopathy which are defined based on age of onset and severity of condition, although there is a high degree of overlap between the conditions. There does not seem to be a correlation between severity of the condition and the gene which has the mutation.
Although heart problems are not common in people with a rod myopathy, it is important that cardiac function is regularly monitored.
The six sub-groups are described in the table below. Sub-group Onset
Clinical signs Severe congenital form
Birth Severe floppiness and muscle weakness
Little spontaneous movement Difficulties with sucking and swallowing
Severe breathing problems
Death usually occurs early
Amish nemaline
myopathy
Birth Floppiness/hypotonia
Contractures/ tightening of joints
Breathing problems
Death usually within 2 years of life
Intermediate
congenital form
Birth Severity in-between severe and mild forms
Early development of contractures/ tightening of
joints
Delayed motor milestones
Independent breathing at birth
Use of ventilatory support and/or wheelchair by
11 years
Typical (mild)
congenital form
Birth →
1 year
Floppiness/ hypotonia
Weakness in muscles closest to trunk, and
sometimes spreading to more distal muscles.
Feeding difficulties
Some respiratory weakness, but less severe
than other forms
Childhood-onset 8 → 15
years
Early motor development normal
Symmetrical weakness of ankle including foot
drop
Slowly progressive weakness with eventual
involvement of all ankle movement.
Motor development normal
Adult-onset 20 → 50
years
Generalised weakness with rapid progression
Muscle pain
Sometimes severe neck weakness
Usually no previous family history

How is it diagnosed?

• Muscle biopsy - Generally, diagnosis is made through a muscle biopsy. A sample of muscle is taken, and examined under a microscope. This is done in one of two ways: either a small piece of muscle is taken under general anaesthetic or a needle biopsy is performed to remove a small sample. Muscle from people affected by nemaline myopathy has a distinctive pattern with thin thread- or rod-like structures in the muscle cells. It is important to note that these structures are also seen in other, unrelated conditions. For this reason, the muscle sample must be considered along with the physical signs and/or molecular tests, in order for a diagnosis of nemaline myopathy to be made. A factsheet on Muscle biopsies is available from the Information and Support Line, or from the website at www.musculardystrophy. org
• Molecular testing - In families where the mutation is known to occur in the gene for α- actin, molecular testing is available. This involves taking a blood sample and analysing the DNA for the presence of a mutation. The gene is “read” from end to end, and this sequence is compared to a normal α- actin sequence. This process can take up to several weeks to complete. Once this error has been identified in one family member, it is possible to use this sequence to diagnose other family members.

What other tests are available?

Prenatal diagnosis - Prenatal diagnosis is available for families where the mutation has been identified as being in the gene for α- actin, and the precise nature of the mutation established. The technique is described in the section Molecular testing, but there are two ways to obtain samples for testing:
• Amniocentesis is traditionally performed at 15 to 17 weeks into the pregnancy. Using ultrasound to visualise, a needle is inserted through the abdominal wall, and a sample of the fluid surrounding the baby (amniotic fluid) is taken.
• Chorionic villus sampling (CVS) is carried out at 10 to 11 weeks. This involves taking a sample of tissue from the placenta. Results are available earlier using this technique than amniocentesis, but the rate of spontaneous abortion is slightly higher.
Carrier testing - As with prenatal diagnosis, carrier testing is currently only available for families where a mutation in the α- actin has been identified and characterised.

How will it progress?

The progression of these conditions is variable, and some may progress more quickly then others. Generally it is accepted that the earlier the onset, the more severe the condition. For children who live beyond the early years, only some will lose the ability to walk. Respiratory function is thought to improve over time, with the most severe problems occurring earlier in life.

Is there a treatment?

There is currently no effective treatment to halt the progression of the nemaline myopathies, but management of the condition is very important for prolonging life.
• Night time ventilation - Breathing problems are common with the nemaline myopathies,
and thus respiratory function should be regularly monitored. A decrease in oxygen intake can lead to, among other things, headaches, breathlessness, poor appetite and disturbed sleep. Night time ventilation involves the use of a face mask attached to a small machine, which assists in breathing. This aids the muscles which control breathing, and allows a greater intake of oxygen. Night time ventilation may be beneficial to people with a rod body myopathy, but this should be discussed fully with a consultant to determine whether it is appropriate.
• Feeding tube (or gastrostomy) - This is a tube that goes into the stomach through the stomach wall and enables a person to be given food and fluids by passing them directly into the stomach via the tube. People with a myopathy may have problems with swallowing which can lead to choking and inhalation of food. This can results in chest infections. A feeding tube prevents this from happening. There are a number of different types of feeding tube which are available, and these are fitted by a short surgical procedure. A factsheet on Gastrostomy is available from the Information and Support Line, or from the website at www.muscular-dystrophy.org
• Physiotherapy - The primary aim of an individual with a neuromuscular disorder is to increase or at least maintain function and mobility. Physiotherapy can assist in doing this, and it can also maintain breathing capacity, delay the onset of curvature of the spine (scoliosis), and help prevent the development of contractures. It is important that the physiotherapist involved is familiar with the treatment of people with neuromuscular disorders.
• Exercise - There is debate over whether people with neuromuscular disorders should undertake strenuous physical exercise. Some say that putting additional strain on already weakened muscles will cause additional harm, whilst others believe that the exercise may increase muscle strength. Insufficient evidence exists to support either, but it is believed that moderate non-weight bearing exercise such as swimming, walking or peddling may be the best solution. This sort of aerobic exercise helps to maintain a healthy cardiovascular system and a steady weight. It is however, important that this is discussed fully with a clinician.
• Antibiotics - Chest infections are common with the nemaline myopathies and complications with breathing can lead to a variety of other problems, including lethargy, headaches, and poor appetite. Antibiotics are used to treat chest infections. There are a variety of antibiotics available, and a GP will be able to advise on the most suitable. If there is a tendency to chest infections it is worth considering pneumovax (prevenar in children under two years) and the flu vaccine.

Is there a cure?

Currently there is no cure for the nemaline myopathies although much research is being currently being conducted into the myopathies, including the rod body myopathies. Although there is no effective treatment to halt the progression, there are a couple of different ways in which to manage the symptoms of the nemaline myopathies and these are outlined above.

What research is currently being done?

Researchers world-wide are exploring many avenues in an attempt to develop more effective treatments and hopefully a cure. The research department at the Muscular Dystrophy Campaign, regularly monitors research advances in the congenital myopathies, and produces releases which are sent to members when significant scientific advances occur.

Planning for the future?

Nemaline myopathies are progressive conditions which means that the needs of individuals with the condition will change with time.

There are a number of things which should be considered:
• Education
• Holidays
• Home adaptations
• Ventilation
• Wheelchairs
More information on any of these topics can be obtained by contacting the Information and Support Line.
Other things to consider
• Anaesthetics - It has now been recognised that the use of both local and general anaesthetics in people with neuromuscular disorders, can cause a variety of different problems. Although anaesthetics are generally well tolerated by people with a nemaline myopathy, due to the nature of the anaesthetic drugs used, problems can include dysfunction of the heart, and relaxation of the muscles round the lungs causing problems with breathing. Generally if a patient is properly assessed and monitored, the risks associated with anaesthetic use are low, but it is very important that the medical professionals involved are fully aware of the muscle condition.
• Medical alert card - It is very important that health professionals are aware of your condition should you require treatment. There are often issues they will have to consider. Many companies are able to provide a Medic Alert Card, which can be carried to advise of any medical condition. These come in the form of bracelets, pendants etc and carry essential information.
• Pregnancy - Pregnancy and delivery are generally well tolerated in mothers with nemaline myopathy. It is however, important to monitor breathing and heart function, and consideration should be given to any muscle weakness of contractures which may complicate the delivery.

Myotubular (centronuclear) myopathy

2010-02-10T14:51:00.000-08:00

Myotubular, or centronuclear, myopathy falls under the umbrella of congenital myopathies. It is characterised by a specific pattern in the muscle tissue when viewed under a microscope. There are three different types of myotubular myopathy, described according to the pattern of inheritance seen. Each of these is very rare. There is currently no effective treatment or cure for myotubular myopathy, but management of the condition is very important and includes physiotherapy, and where necessary the use of ventilation and/or a feeding tube.

What is myotubular myopathy?

Myotubular, or centronuclear, myopathy belongs to the family of congenital myopathies which are characterised by muscle weakness. Congenital means “from birth” and myotubular myopathy is generally apparent very early in life. Myotubular myopathy is so named because of the presence of structures that look like myotubes, immature muscle cells.

What causes it?

There are three different types of myotubular myopathy each defined by the pattern of inheritance seen. There are also sporadic cases where there is no previous family history, but the prevalence of these has not yet been determined. X-linked myotubular myopathy (or XMTM) -This is the most common form of myotubular myopathy, and is caused by an error in the myotubularin (MTM1) gene which produces a protein called myotubularin. This protein is known to be required in m uscle development, for the formation of adult muscle.
The MTM1 gene is located on the X chromosome. Individuals have 46 chromosomes, two of which are called the sex chromosomes. Females have two copies of the X chromosome whilst males have one copy of X and one copy of the Y chromosome. If a female has an error on one copy of her X chromosomes, usually she will have enough protein from the “good” chromosome to compensate for the error, and will not have the condition. Manifesting carriers are the exception to this rule (see later section).
If males have the error on their X chromosome, they have no “good” gene to compensate and they will have the condition.
Autosomal dominant myotubular myopathy - This pattern of inheritance is very rare and only a few families have been described with this condition. The gene abnormality causing the condition was very recently identified by researchers in Paris; it is called the Dynamin 2 gene (DNM2). Autosomal dominant inheritance means that only one copy of the genetic error is needed to cause the condition, and one good copy cannot compensate. This form of the condition affects both males and females.
Autosomal recessive myotubular myopathy -This pattern of inheritance is also very rare. As with the autosomal dominant form, the gene involved has not been identified, but is expected to have a similar function to the myotubularin gene.
Autosomal recessive means that, in order for a person to be affected, he or she must have two copies of the genetic error. Each parent must carry a copy of the error, but usually they do not show any signs of the condition. This form of the condition also affects males and females.

What are the common features?

X-linked myotubular myopathy (or XMTM) - This is the most severe form of myotubular myopathy. It generally affects only males, and has the earliest onset. Commonly there are signs of the condition before the baby is born, and often an excessive accumulation of amniotic fluid around the baby is seen. Most individuals are born with severe floppiness (hypotonia), muscle weakness, and infants may fail to breathe spontaneously at birth, most will require breathing support. There are usually problems with feeding, in particular swallowing, and breathing problems can persist. Chest infections may occur frequently. The child may have a long face, which could seem expressionless. The eyelids may be puffy, and some of the muscles in the eyes may not function correctly. There may be tightening of the knee and ankle joints (contractures).
The severity of the condition varies considerably. In many cases death occurs in the first few months. Some children who survive infancy may show improvement in the first few years, although many will be severely disabled. Many of these children will require ventilatory support to assist their breathing. Occasionally, some children improve significantly and are left with only mild residual weakness even into adulthood.
Female manifesting carriers of XMTM - Manifesting carriers of myotubular myopathy are very rare. As mentioned earlier, every female has two copies of the X chromosome. In every cell, one copy is “switched off”. Usually this is random, but in some exceptional cases, more copies of the “good” chromosome are inactivated. In such cases a female may show signs of the condition, but this is likely to be only mild weakness. Autosomal recessive myotubular myopathy - This is the intermediate form, with onset occurring in infancy or early childhood. Weakness of the muscles in the face may occur, as may droopiness of the eyelids. Some people may have problems with feeding. There is usually weakness of the proximal muscles (those closest to the trunk of the body).
Autosomal dominant myotubular myopathy - Onset of this form is very variable, ranging from birth to 30 years. It is not as severe as X-linked, and the condition generally follows a mild course. There is weakness of the muscles closest to the trunk of the body, although some people may show weakness of the more distal muscles. A problem with the heart has been seen in one person previously, and so is rare. It is, however, important to regularly monitor heart and lung function.

How is it diagnosed?

The clinical signs are usually the first indication that there is a problem with the muscles. In order to confirm the diagnosis a muscle biopsy is required. Muscle biopsy - This is done in one of two ways: either an open biopsy where small piece of muscle is taken under general anaesthetic or a needle biopsy is performed under local anaesthetic to remove a small sample. The sample will be analysed under a microscope. Muscle from people affected by myotubular myopathy shows a characteristic pattern, similar to that seen in foetal muscle. The nuclei are centrally located (hence the name centronuclear) instead of being at the outer edges of the fibres. A factsheet on muscle biopsies is available from the Information and Support Line (contact details are shown below).
• Molecular testing - This is only available for X-linked myotubular myopathy, testing for the dynamin mutation will become available in the future. It seems likely that the genetic cause for the X linked form will be identified in the future. DNA testing involves taking a blood sample and analysing the DNA for the presence of a mutation. The gene is either “read” from end to end, and this sequence is compared to a normal MTM1 sequence, or only certain sections of the gene are analysed. This process can take up to several weeks to complete. Once this error has been identified in one family member, it is possible to use this sequence to diagnose other family members.

What other tests are available?

Prenatal diagnosis is available for families that are known to have a history of X-linked myotubular myopathy. The technique is described in the section Molecular testing, but there are
two ways to obtain samples for testing:
• Amniocentesis is traditionally performed at 15 to 17 weeks into the pregnancy. Using ultrasound to visualise, a needle is inserted through the abdominal wall, and a sample of the fluid surrounding the baby (amniotic fluid) is taken.
• Chorionic villus sampling (CVS) is carried out at 10 to 11 weeks. This involves taking a sample of tissue from the placenta. Results are available earlier using this technique than amniocentesis, but the rate of spontaneous abortion is slightly higher. Carrier testing - As with prenatal diagnosis, carrier testing is currently only available for families known to be affected by the X-linked form of myotubular myopathy.

How will it progress?

Myotubular myopathy is a non-progressive or slowly progressive condition. However, infants with X-linked myotubular myopathy may progress into respiratory failure rapidly and the majority of those who survive beyond infancy are dependent on artificial respiration. The autosomal forms are usually less severe.

Is there a treatment?

There is currently no effective treatment for myotubular myopathy, but management of the condition is very important for prolonging life.
• Night time ventilation - Breathing problems can occur with myotubular myopathy, and thus respiratory function should be regularly monitored. A decrease in oxygen intake can lead to, among other things, headaches, breathlessness, poor appetite and disturbed sleep. Night time ventilation involves the use of a face mask attached to a small machine, which assists in breathing. This aids the muscles which control breathing, and allows a greater intake of oxygen. Night time ventilation may be beneficial to people with myotubular myopathy, but this should be discussed fully with a consultant to determine whether it is appropriate.
• Feeding tube (or gastrostomy) - This is a tube that goes into the stomach through the stomach wall and enables a person to be given food and fluids by passing them directly into the stomach via the tube. People with a myopathy may have problems with swallowing which can lead to choking and inhalation of food. This can result in chest infections. A feeding tube prevents this from happening. There are a number of different types of feeding tube which are available, and these are fitted by a short surgical procedure. A factsheet on gastrostomy is available from the Information and Support Line.
• Physiotherapy - The primary aim of an individual with a neuromuscular disorder is to increase or at least maintain function and mobility. Physiotherapy can assist in doing this, and it can also maintain breathing capacity, delay the onset of curvature of the spine (scoliosis), and help prevent the development of contractures. It is important that the physiotherapist involved is familiar with the treatment of people with neuromuscular disorders.
• Exercise - There is debate over whether people with neuromuscular disorders should undertake strenuous physical exercise. Some say that putting additional strain on already weakened muscles will cause additional harm, whilst others believe that the exercise may increase muscle strength. Insufficient evidence exists to support either, but it is believed that moderate non-weight bearing exercise such as swimming, walking or peddling may be the best solution. This sort of aerobic exercise helps to maintain a healthy cardiovascular system and a steady weight. It is however, important that this is discussed fully with a clinician.
• Antibiotics - Chest infections are common with myotubular myopathy and complications with breathing can lead to a variety of other problems, including lethargy, headaches, and poor appetite. Antibiotics are used to treat chest infections. There are a variety of antibiotics available, and a GP will be able to advise on the most suitable. If there is a tendency to chest infections it is worth considering pneumovax (prevenar in children under two years) and the flu vaccine.

Is there a cure?

Currently there is no cure for myotubular myopathy although much research is being conducted into the congenital myopathies, including myotubular. Although there is no effective treatment for the condition, there are a couple of different ways in which to manage the symptoms of myotubular myopathy and these are outlined above.

What research is currently being done?

Researchers world-wide are exploring many avenues in an attempt to develop more effective treatments and hopefully a cure. The research department at the Muscular Dystrophy Campaign, regularly monitors research advances in the congenital myopathies, and produces research updates, which are sent to members when significant scientific advances occur.

Planning for the future?

Myotubular myopathy, although thought to be non-progressive, may change with time, especially as the child grows. This means that the needs of individuals with the condition may change over time.
There are a number of things which should be considered:
• Wheelchairs
• Home adaptations
• Education
• Ventilation
• Holidays
More information on any of these topics can be obtained by contacting the Information and Support Line.

Other things to consider

• Anaesthetics - It has now been recognised that the use of general anaesthetics in people with neuromuscular disorders, can cause a variety of different problems. Although anaesthetics are generally well tolerated by people with myotubular myopathy, due to the nature of the anaesthetic drugs used, problems can include dysfunction of the heart, and relaxation of the muscles round the lungs causing problems with breathing. Generally if a patient is properly assessed and monitored, the risks associated with anaesthetic use are low, but it is very important that the medical professionals involved are fully aware of the muscle condition.
• Medical alert card - It is very important that health professionals are aware of your condition should you require treatment. There are often issues they will have to consider. Many companies are able to provide a Medic Alert Card, which can be carried to advise of any medical condition. These come in the form of bracelets, pendants etc and carry essential information.
that provide alert cards.

Myotonic dystrophy

2010-02-10T14:46:00.000-08:00

What is myotonic dystrophy?

People with myotonic dystrophy, like those with other dystrophies, experience muscle weakness and wasting which is usually progressive. There are many differences, though, in the type of problem that people with myotonic dystrophy may have. These may include the following: Types of muscles involved are usually in the face, jaw and neck area; the large, weight-bearing muscles of the legs and thighs are much less affected.
Rate of deterioration is commonly slow, with little change over a long period; some people never have significant muscle disability. Muscle stiffness or 'myotonia' is characteristic, especially affecting the hands. Involvement of other body systems is frequent; associated problems may include cataracts, disturbance of heart rhythm, hormonal problems and, in children, learning difficulties. Age at onset is very variable. Symptoms may appear at any time from birth to old age.

How is myotonic dystrophy inherited?

This condition follows a 'dominant' inheritance pattern, which means that on average half of the children of an affected person are themselves affected. Both men and women are equally likely to be affected and to pass on the disorder, but affected women are more likely to have a severely affected child. In general (though not always) the disorder tends to be more severe in successive generations.
Most healthy adult relatives will not be likely to develop or pass on the disorder, but a careful assessment by an expert is important as mild features can easily be missed. Genetic testing on a blood sample for such relatives can now provide greater certainty, but should always be done with full information as part of genetic counselling. Genetic testing of healthy young children is not recommended.
Very few cases of myotonic dystrophy occur 'out of the blue'. Almost always, one parent proves to be affected, often very mildly. Some parents (or grandparents) prove to carry a very slight genetic change that will never give them symptoms. Careful study of the whole family often shows more members to be affected than would appear likely at first.

What is the cause?

The changes in muscle and other body systems in myotonic dystrophy are now known to result from a specific genetic change (mutation) which in most cases involves a gene on chromosome number 19. The same change occurs in patients world-wide, but it is variable in extent, even in a single family, because it is unstable. The length of a particular ‘triple repeat sequence’ (CTG) is expanded in patients and this may vary from a slight expansion in mildly affected individuals to a very large one in severely affected children. Until recently it has not been clear how genetic change causes the condition: the most likely mechanism is now thought to be that the expanded repeat is converted normally into the next stage (RNA), but then is unable to leave the cell nucleus. As a result of this trapping, a range of other types of RNA are affected, as are the protein they produce, which helps explain how a single genetic change can affect different body processes.
‘PROMM’ (proximal myotonic myopathy) and type 2 myotonic dystrophy. An important recent advance is the recognition of a second disorder with features resembling myotonic dystrophy.The muscle weakness tends to differ in distribution (more in proximal limb muscles, less in the face) and myotonia is often mild or absent. Cataract and heart involvement occurs as in myotonic dystrophy. It is now clear, that this condition (PROMM: proximal myotonic myopathy), is the same as some rare families thought, clinically, to have myotonic dystrophy but
not showing the expected mutation and termed ‘type2 myotonic dystrophy’ or ‘DM2’. The gene involved has now been isolated on chromosome 3. Although quite different to that for myotonic dystrophy it contains a very similar, expand repeat (CCTG), which is likely to explain the clinical similarity of the two disorders. We are still learning about the details of this condition, but it is probably uncommon and accounts only for a small proportion of patients thought clinically to have myotonic dystrophy.

Future advances

The research advances of the past 10 years have increased our understanding to the point where we can begin to see future possibilities for preventing or limiting the damage to muscle and other systems that occurs in myotonic dystrophy. In particular the genetic changes can now be re-produced in mouse models, which could allow the study of the effects of drugs and other agents that might be too untried to use safely on humans initially. It is difficult to predict howrapidly this work will progress, but possibilities exist now that were not present until very recently.

Problems and management

Although no 'cure' for myotonic dystrophy exists at present, there is a lot that can be done to help those affected. Indeed, since many doctors are unfamiliar with the condition, it is essential that people who have myotonic dystrophy are themselves aware of the problems and dangers they may face. Some of these are mentioned here; of course they rarely all occur in one person, and many people have few symptoms, but it is important to be aware of them. Operations and anaesthetics can be risky, even for mildly affected people. It is most important that any surgeon or anaesthetist should know a person has myotonic dystrophy before surgery is planned. Problems usually occur when doctors are unaware of the disorder; if care is taken, surgery is usually safe. A person may wish to wear a bracelet or locket stating their condition. A specific warning card is available that can be carried in a wallet. This can be obtained from the Myotonic Dystrophy Support Group (address below). 'Keep out of trouble' is a good motto for those with myotonic dystrophy. A minority of people can develop heart problems, which are commonly treatable but can be serious if ignored. A regular cardiogram (ECG) is wise.
Some people who have myotonic dystrophy may have more trouble with other body systems than they do with their muscles. A symptom that appears quite unrelated may be connected.
Excessive daytime sleepiness, swallowing difficulties and a range of bowel symptoms are examples. It is important that people with myotonic dystrophy should make sure that whoever treats them is aware that they have the condition and knows the wide range of associated problems.
If troublesome, muscle stiffness due to myotonia can be helped with certain drugs. Children with myotonic dystrophy may have learning problems at a time when there are no muscle complaints. Again, be sure that myotonic dystrophy is borne in mind if this disorder is in the family. Affected women need careful management if undertaking a pregnancy. Not only is there a risk of a baby being severely affected, but problems in pregnancy and delivery may affect the mother.
Equipment for mobility and adaptations in the house can be very useful, though few affected people need a wheelchair. Weak neck muscles make a sound head-rest essential when driving.

In summary

In summary, we now know a lot about myotonic dystrophy, but still have a long way to go. Helpful genetic counselling and family testing are now possible, but the best approach to treatment is to know about the condition, its risks and complications, and to be sure that your doctors do too.

The Myotonias

2010-02-10T14:42:00.000-08:00

What is myotonia?

Myotonia refers to the condition in which muscles are slow to relax after contracting. It occurs in
a number of diseases such as myotonic dystrophy, myotonia congenita and paramyotonia congenita. However myotonic dystrophy is a very distinct condition in which myotonia is only a part. For this reason, and also because it is relatively common, there is a separate leaflet dealing specifically with this disorder. In the other two disorders myotonia is the main and often only symptom. They are the subjects of this leaflet.

Myotonia congenita

The principal complaint in myotonia congenita is failure of muscle to relax normally after contracting; this can be severe enough to interfere with normal everyday activities. Myotonia most often occurs after long periods of rest, for example on waking in the morning, or on standing up and starting to walk after prolonged sitting. Most often it affects the limb muscles making walking and climbing stairs difficult. The face may also be affected and opening the eyelids can sometimes be difficult. Stiffness may not only occur after prolonged rest, but can often be brought on by cold, fatigue or emotional stress. It is relieved by exercise and is generally not accompanied by pain. One problem, which can be serious, is after a sudden movement, for example turning quickly to avoid traffic while crossing the road; the muscles tend
to remain stiff and the individual may fall down as a result. Apart from myotonia, muscle enlargement, which may be pronounced, often occurs and affects the calves, thighs, shoulders and forearms.

How is myotonia congenita inherited?

There are two types of myotonia congenita, both of which are inherited. The commoner type (the so-called Becker type) is inherited as an autosomal recessive trait (Becker myotonia congenita). In this case there is a 1 in 4 chance that any brother or sister may be affected, but affected individuals themselves are very unlikely to have affected children. In this form of myotonia, symptoms are often first noticed in late childhood and may then progress until adulthood when there may also be some degree of muscle weakness. Muscle enlargement can be marked.
The less common form is inherited as an autosomal dominant trait (Thomsen myotonia congenita) when there is a 1 in 2 chance of an affected parent transmitting the disease to any child he or she may have. In this form of myotonia, symptoms first appear in early childhood, often in infancy, and parents may notice that when their baby cries the eyes remain closed for an unusually long time. However, myotonia is mild and does not become more severe with time.
Treatment is not usually necessary.

What is the cause?

The underlying genetic fault in both the autosomal dominant and recessive forms of myotonia congenita causes a structural change in the channel (or pore) in the muscle cell wall that lets in chloride ions. Chloride ions help muscle to relax after contraction and the damaged chloride ion channels in myotonia congenita let in too few chloride ions for efficient relaxation.

Can it be treated?

Many affected individuals learn to cope with their disability by working off the myotonia through repeated movements and avoiding the cold as much as possible. When severe, myotonia can be relieved by certain drugs (such as mexiletine) which can be prescribed by the doctor.

Paramyotonia Congenita

In this condition myotonia evident from early childhood, is generalised but particularly affects the face and hands, and characteristically is aggravated by, or only occurs on exposure to, cold. It
is not progressive and usually does not require treatment. Often muscle stiffness may actually be made worse by exercise, especially in cold weather. For this reason myotonia in paramyotonia congenita is referred to as "paradoxical" because repetitive activity often makes it worse rather than better. The condition is inherited as an autosomal dominant trait.
Here the defect is in so-called sodium ion channels in the muscle membrane. A few patients may experience periodic paralysisa sudden ‘floppy’ weakness of one or more limbs that can last minutes or hours. Episodes can be brought on by certain foods or drinks rich in potassium (e.g. bananas, orange juice), resting after exercise, missing meals or an infection.

Other forms of Myotonia

Other rarer forms of myotonia have also been described, including one type in which prolonged attacks of weakness may occur. Because the myotonias are an uncommon group of disorders with differing severities and modes of inheritance, it is important to seek advice from a neurologist or medical geneticist with particular knowledge of these conditions.

Myopathy

2010-02-10T14:36:00.000-08:00

A fact sheet for parents whose child has had a muscle biopsy that confirms a myopathy. Adults with a myopathy may also find it helpful.

What is a myopathy

We look at the muscle biopsy under the microscope for evidence of damage. Some changes suggest that the problem is not with the muscle itself, but with the nerve that controls that muscle and we call this neurogenic. Other changes suggest that the problem is with the muscle itself, and this appearance is called myopathic. When certain specific features are present we use the term dystrophic rather than myopathic.

Why do biopsies?

We do muscle biopsies to be able to see what is going on in the muscle and to see if we can discover what is causing the problems that your child is experiencing. This will then allow us to be aware of any possible, future problems. In an abnormal muscle biopsy there is more variation in fibre size and more irregularities in the muscle fibre than in normal muscle.
However, contrary to what is found in dystrophic processes, there are no significant signs of damage or scarring. This may be an important distinction because the kinds of conditions that are associated a myopathic process in the process are different to the kinds that are associated with dystrophic changes, which can indicate more severe muscle damage.

What causes a myopathy?

There are many different underlying causes of a myopathic biopsy.
If a muscle looks myopathic, there may be special features present, like ‘cores’ or ‘rods’ in the muscle which then point to an even clearer diagnosis than just a ‘myopathy’, but in many cases there are no specific features or clues that will point to a particular type of myopathy. In these situations it can take us a long time to work out the exact cause of the problem.

Is it possible that in the future they may be a more specific diagnosis?

When we do not come up with an exact diagnosis straight away, we continue to look at the biopsy using more specialised tests, as and when they become available, this process may take several years. We can also learn from follow-up appointments how things develop at the clinical level, and this can give us clues as to what is happening to your child. Sometimes, later on, we need to do a further biopsy as this can occasionally show up features, which were not present on the initial biopsy, but this will need to be discussed at the time.

What problems should I be aware of?

It is frustrating for parents who, when planning their child’s future, do not know the exact cause of their child’s myopathy; however, there are the things we have to look after. It is important to realise that not al of the following problems may come up in an individual child, but because there is a risk of these kinds of issues we must be aware and be careful to watch out for: Muscle weakness. The weakness in the muscles in patients with myopathy is often fairly non-progressive, but can lead to problems with the range of movement of the joints or with the back. This means that we need to keep a close eye on mobility and joints and we do this in conjunction with the local physiotherapy team as well as through the muscle clinic. People with myopathies can have chest problems because their cough is not strong. Where this may be a problem, we will be recommending the flu and pneomax immunisations. We also keep a close eye on your child’s chest and teach some specialised physiotherapy techniques to help him cough. If your child becomes ill with a chest infection, it is important this is treated promptly. Feeding difficulties can also be an issue, and if someone is not eating or feeding very well then that can lead to undernutrition. You will need to be aware of this. Some people with a myopathy can also have problems with constipation, which can be managed in the usual kinds of ways. To ensure that a child is getting the help he or she needs, support and information to schools and other professionals may be necessary. You may have other questions about the long term implications of this condition on your child’s health. It is very difficult to generalise about this, for children with a myopathy may be very different from one another. This is something that is best discussed with your local doctor. As time goes by there may be other issues which come up and these will be all be dealt with, in partnership with the local services, when you come to the muscle clinic.

Myasthenia Gravis

2010-02-10T14:26:00.000-08:00

What is Myasthenia Gravis?

Myasthenia Gravis (MG) is a chronic, autoimmune disease that causes muscle weakness and excessive muscle fatigue. It is uncommon, affecting about 15 in every 100,000 individuals in the UK. The disease can vary in severity and distribution of weakness between individuals, and in any one patient the symptoms fluctuate with relapses and remissions. MG can resolve spontaneously, but for most patients MG persists for life. It can be life threatening, but 90% of patients become symptom-free with modern treatments.

Who is at risk of developing MG?

MG affects all races and can develop at any age from childhood to extreme old age. Young patients are more commonly women, whereas older patients, over 50 years, are more often men. People who inherit a tendency to develop autoimmune disease are at increased risk of developing MG, so a patient with MG may have another autoimmune disease, such as diabetes or thyroid disease, or have a relative with autoimmune disease. Occasionally MG develops in patients with rheumatoid arthritis who are given the drug penicillamine. In these cases, the MG symptoms usually disappear when the drug is stopped.

Is MG hereditary?

MG is not an inherited disease and does not usually occur in families. This is in contrast to the congenital myasthenic syndromes that are genetic disorders (see below). However, it is thought that an individual¡¦s genetic make-up is one factor, of perhaps many, that leads them to develop MG, and it may occasionally be found in more than one family member.

What are the symptoms of MG?

The hallmark of MG is weakness of voluntary muscles, which gets worse with repeated or sustained use of the muscle (fatiguable muscle weakness). Symptoms fluctuate and are typically worse at the end of the day, in hot weather, during or immediately after an infection, or during menstruation. In two thirds of patients with MG, the first muscles to be affected are those controlling eye and eyelid movements, and almost all patients have involvement of these muscles at some stage. In some patients, the MG only ever involves the eye muscles (ocular MG) while in the majority there is also involvement of other muscles (generalised MG). MG itself does not cause pain, but the weakness may lead to non-specific aches and pains. For instance, neck pain may occur because of weakness in the neck muscles.

What causes MG?

MG develops in adult life as the result of a defect in the immune system. The immune system job is to produce antibodies against bacteria and viruses. Unfortunately, it sometimes produces antibodies against ¡§self¡¨ proteins causing ¡§auto¡¨immune disease. The majority of patients with
MG produce antibodies against a self-protein called the acetylcholine receptor (AChR). This is found at the junction between the nerve and the muscle (the neuromuscular junction (see figure 1 & 2). It acts as a ¡§receiver¡¨ for the chemical signal, acetylcholine that is released from the nerve when we want to use a muscle. The antibodies bind to the acetylcholine receptors on the muscle membrane and greatly reduce their ability to receive the chemical signal. As a result the patient experiences muscle weakness which becomes worse as they repeatedly try to use the same muscle. Although we now understand how antibodies to the acetylcholine receptor cause muscle weakness, we do not know why patients with MG develop these particular antibodies. In some patients with MG, the thymus gland in the chest appears to be important in triggering the abnormal immune response.

Fig. 1 Below: The normal neuromuscular junction
Fig. 2 Below: The neuromuscular junction in Myasthenia Gravis (MG)
The diagram shows the chemical signal, acetylcholine, and the receivers, acetylcholine
receptors. The inverted Y shaped molecules are antibodies binding to the acetylcholine
receptors and preventing them from working.

Is MG all the same disease?

MG presents in two main forms:
OCULAR MG affects the eye muscles only.
1) Drooping of the eyelids (ptosis) is often intermittent, and can affect one or both eyes
2) Double vision (diplopia) may be intermittent, and sometimes occurs only when looking in a
particular direction.

GENERALISED MG patients usually have symptoms of ocular MG but there is also involvement
of:
1) Face and throat muscles, affecting smiling, speech (dysarthria), chewing and swallowing
(dysphagia).
2) Neck muscles, causing difficulties in holding the head up.
3) Limb muscles, causing difficulties in walking upstairs, and in holding the arms up (e.g. when
brushing hair).
4) Breathing muscles, causing shortness of breath when exercising or when lying flat.

How is MG diagnosed?

The history and examination of the patient can suggest the diagnosis but it is important to confirm the diagnosis by special investigations:
Antibodies to the acetylcholine receptor are found in 85% of patients with generalised MG, and 50% of patients with ocular MG. They are detected by a blood test.
Electromyography (EMG) is performed by a specialist doctor and involves measuring the electrical response in the muscle with a very fine needle. An electrical stimulus is applied to a nerve and the response in the muscle is recorded. It is a very sensitive test, showing an abnormality in most patients with MG, but is not available at all hospitals.
TensilonR test, an injection of Edrophonium is given which results in a rapid but short-lived improvement in symptoms in many patients.
Chest scan should be done to check whether the thymus is abnormal as many patients with MG have an enlarged thymus, and some have a benign tumour.

What else could it be?

The key feature that differentiates MG from many other diseases is the fatiguable character of muscle weakness and fluctuating nature of the symptoms. Diseases affecting the muscles themselves (e.g. mitochondrial cytopathy or muscular dystrophies) can cause several of the symptoms seen in MG, and the eye symptoms can present in-patients with thyroid disease.
There are other even rarer diseases that can be confused with MG and which are described briefly below.

What will the doctor do?

Since MG is uncommon, the General Practitioner usually refers the patient to a specialist neurologist for further assessment and tests, and for initiation of treatment. Once the diagnosis has been made the General Practitioner has a very important role in prescribing and monitoring the medication.

What can the patient do themselves?

Patients should use common sense and avoid things that would put them in danger if their weakness suddenly increased (for instance swimming on their own). Taking medications regularly is the key to maintaining the lowest possible levels of symptoms.

Can women with MG have babies?

Many women with MG develop the disease as teenagers and the disease is well controlled before they want to have children. The MG symptoms sometimes get worse during pregnancy but equally often get better. Sometimes the baby is born with a transient form of MG, due to the transfer of antibodies across the placenta, but these symptoms respond well to treatment and usually disappear within days to weeks causing no permanent disability. On very rare occasions, an untreated mother may give birth to a baby with severe symptoms, (including joint deformities) requiring intensive care. This has never been reported in a mother who has been diagnosed and adequately treated for MG.

What is the treatment?

Anti-cholinesterase medication
The first specific form of treatment is anti-cholinesterase drugs (usually one called Pyridostigmine), which prevent the breakdown of acetylcholine and so improves the efficiency of
the chemical signal at the neuromuscular junction. The benefits of Pyridostigmine occur within 30-60 minutes, but wear off in 3-4 hours, so tablets should be taken at regular intervals throughout the day. Patients may develop colicky abdominal pain and diarrhoea on Pyridostigmine, because the medication also increases nerve and muscle action in the intestine.
If this occurs the dose can be reduced, or alternatively Propantheline can be taken 30 minutes before each Pyridostigmine dose to counteract the effects on the bowel. For some patients MG symptoms disappear with Pyridostigmine alone, but most require additional treatments, which vary for each patient.

Thymectomy

Since the thymus can be abnormal in-patients with MG, surgical removal of the thymus (thymectomy) is recommended for some patients. Following thymectomy, MG symptoms do not
usually improve in-patients with a thymoma, but may improve in young patients with an enlarged thymus. In these patients, approximately 1 in 4 are cured by thymectomy, 2 in 4 have significant improvement, but 1 in 4 do not improve. Improvement following thymectomy is usually apparent in the first year, but may take up to 3 years to occur. If the patient recovers, or improves significantly following thymectomy, then they may not need any additional therapy. But many patients will need further treatments.

Immunosuppression:

„h Steroids. Patients who do not respond to thymectomy, or do not undergo a thymectomy, are treated with steroids. Patients are usually started on a low dose of steroids, which is gradually increased over the next few weeks to reach the full dose. During this period the patients are often kept in hospital as symptoms sometimes deteriorate before they improve. Once the symptoms are controlled, the dose of steroids is gradually reduced to find the minimum dose at which the symptoms remain under control. Patients then remain on that dose. There are several side effects associated with steroids, some of which can be prevented by taking additional medication. Thinning of the bones (osteoporosis) can occur and so patients will have a bone densitometry (DEXA) scan and will have medication to protect the bones if appropriate. Patients should never stop taking steroids suddenly, as this can result in a serious condition because the body has become used to regular steroids. All patients should carry a ¡§steroid card¡¨ so that in an emergency other doctors will know that they require regular steroids. „h Steroid-sparing agents. Although steroids are extremely effective in controlling MG, there are potential side effects. Therefore, additional drugs are often used which allow the doctors to reduce the dose of steroids required and may even allow the patient to stop steroids completely. These drugs also suppress the immune system but they act in a different way to the steroids, take longer to work and have different side effects.
Thus by using a small dose of steroids and one of these other medications, the side-effects are kept to a minimum, while maximising the immunosuppressive effect. Azathioprine is the only steroid- sparing agent that has been tested formally and found to be beneficial in treating MG. However in-patients who cannot take Azathioprine, alternatives such as Methotrexate or Cyclosporin appear to be effective. Patients taking steroids or steroidsparing agents are at increased risk of infection. It is best for patients to consult their doctors before having any vaccinations (live vaccines should be avoided), or engaging in unusual activities that could put them at risk of contracting infections.

Emergency treatments

If a patient is very weak or is having trouble with breathing or swallowing then they are usually admitted to hospital for more aggressive treatments such as plasma exchange or intravenous immunoglobulin (IVIg). These treatments can produce a rapid improvement in symptoms but the benefits only last for about 6 weeks. They are reserved for situations when symptoms need to be controlled quickly, and they are not appropriate long-term treatments.

What is the prognosis?

The prognosis of MG has improved significantly with the introduction of immunosupressive therapy. The majority of patients become symptom free if they are adequately treated. However most patients do have to remain on tablets for life as the symptoms generally return if they stop the medication.

What other diseases can be mistaken for MG?

MG is the most common of the neuromuscular junction conditions, but about 3 in 20 of patients presenting with symptoms of MG will not have antibodies to the acetylcholine receptor. Some of these will have antibodies to another muscle protein, called MuSK. MuSK antibody myasthenia is treated in much the same way as the usual form of MG, although thymectomy may not be needed. Some will have the Lambert Eaton myasthenic syndrome. In this condition, the patients are also weak and fatigue easily, but eye symptoms are less common. About half the patients are smokers and a particular type of lung cancer may be found. Antibodies to another neuromuscular junction protein, the voltage-gated calcium channel, cause the disease. Treatment is similar to that for MG but thymectomy is not performed. There are also rare congenital myasthenic syndromes, which are due to hereditary gene mutations in the acetylcholine receptor. Antibodies do not cause these and thymectomy and immunosuppressive drugs are not used.

Mitochondrial Myopathies

2010-02-10T14:19:00.000-08:00

What are mitochondrial myopathies?

Mitochondrial myopathy is a collective term for a group of diseases that particularly affect muscle, but which may also affect every other part of the body including the brain and the eye.
Other names for these diseases include: Kearns-Sayre Syndrome (KSS), Chronic Progressive External Ophthalmoplegia (CPEO), Mitochondrial Encephalopathy, Lactic Acidosis, and Strokelike
Episodes (MELAS), Myoclonus Epilepsy Associated With Ragged-Red Fibres (MERRF), Leigh’s disease, and Mitochondrial Cytopathy.

Why do I have it?

Our bodies are made up of many different tissues, for example muscle, nerve, and liver. Each tissue is composed of small ‘building blocks’, called cells, and within each cell are small objects known as mitochondria. The job of these mitochondria is to produce energy. Just like a power generator, they take in fuel (the food we eat) and burn it up to generate energy. If this process fails, the cell cannot function adequately and this can lead to disease. Muscle and brain require a lot of energy, and are often the most severely affected.
The part of mitochondria concerned with energy production is called the respiratory chain.
Components (called proteins) of this respiratory chain pathway are produced from a genetic blueprint (the DNA) found either within the mitochondria themselves (mtDNA), or on the chromosomes in what is called the nucleus of the cell. Many mitochondrial diseases, even though they involve the mitochondrial DNA, are sporadic. This means that only one individual in a family is affected – the parents and any children of that person are unaffected. Other mitochondrial diseases are only inherited from the mother. Diseases that arise because of defects within the genes found on chromosomes within the nucleus may be inherited from either parent.

How did they diagnose me?

When the doctor examines you, certain things may raise the possibility of a Mitochondrial Myopathy, for example droopy eyelids (ptosis), or difficulty moving the eyes (ophthalmoplegia), there is a separate Muscular Dystrophy Campaign (MDC) fact sheet covering Ocular Myopathies. A blood test may show a raised lactic acid level. The final diagnosis often depends on taking a muscle biopsy – where the doctor removes a small piece of muscle for further laboratory tests. Under the microscope, mitochondria from people with mitochondrial myopathies often look abnormal, and they accumulate around the edges of muscle fibres giving the so-called ‘ragged red’ appearance. It is also possible to make measurements of how well the respiratory chain functions and identify where the defect lies. In some cases it is possible to establish the diagnosis by looking for the defect (we call the mutation) in the genetic blueprint (either mtDNA or nuclear DNA).

What happens to people with mitochondrial myopathies?

Mitochondrial myopathies affect people in different ways. The most common problem is a combination of mild weakness of the arms and legs together with droopy eyelids (ptosis) and difficulty in moving the eyes (ophthalmoplegia). Others only have weakness of the arms and legs, which gets worse after exertion. This may be associated with nausea and headache. If the illness is severe, muscle weakness may be obvious in small babies, and they may have difficulties with swallowing and feeding. Less commonly, some of these conditions affect the brain. This can lead to epilepsy (fits) and progressive loss of memory. Not all individuals with brain involvement (called encephalopathy) get worse, but some will. The light-sensitive membrane at the back of the eye (the retina) is often affected (abnormal pigment accumulates) and hearing difficulties are common. In addition the heart may be affected requiring the insertion of a pacemaker - an electrical device that helps the heart to beat properly.

Is the condition life threatening and is my life span going to be affected?

The most common mitochondrial myopathy, Chronic Progressive External Ophthalmoplegia (CPEO), is usually only a mildly disabling disorder with normal lifespan, whilst others, that begin early in life, are life threatening. Some, such as Leber’s Hereditary Optic Neuropathy (LHON), affect only vision. The presence of epilepsy, heart involvement and breathing difficulties are all associated with greater risk.

Is there a treatment or cure?

There are no miracle cures. Many of the problems associated with mitochondrial myopathies can, nevertheless, be treat effectively. For instance, diabetes can be treated with tablets or insulin; pacemakers are very effective for the disturbances of heart rhythm. Muscle fatigue can be improved by regular gentle exercise. A few patients improve on treatment with specific vitamins such as ubiquinone, but most do not.

Are there any special risks involved?

Energy demand increases when we are ill. Fasting, either voluntarily or because of illness, also increases the demand put on mitochondria. Regular intake of calories during the day is, therefore, important. If this becomes difficult, particularly during illness and/or if the patient is a
young child, you should contact your doctor. Certain drugs may affect mitochondrial function, and we generally recommend avoiding alcohol. If in doubt you should consult your doctor.

Are any other members of my family at risk?

Recent research has provided a lot of information about the genetic aspects of mitochondrial myopathies and the risk to other family members depends on the precise diagnosis. Most people with mitochondrial myopathies do not have similarly affected relatives, but these are reported in about 20%. Mitochondrial myopathies can be inherited (passed from parent to child) and the genetic error (mutation) can affect either the mitochondrial DNA or the genes found in the nucleus. In those individuals with defects in mtDNA, inheritance will be through the mother whilst for those defects affecting genes in the nucleus either parent may be able to transmit the condition.

What if I want another baby? Can I avoid passing a faulty gene on to my child?

This is a complex question and the advice will vary depending on both the individual and the type of disease (for example whether it is transmitted from the mother or the father). In cases where the disease comes from the mother, the use of eggs (oocytes) from an unaffected donor eliminates the risk of transmission, though of course the donor should not be a maternal relative such as a sister. It is possible in certain types of mitochondrial myopathy, to analyse the baby’s placenta (CVS), or even the very early embryo (pre-implantation diagnosis), but this is neither widely available nor applicable to all of these disorders.
Your local genetics clinic should be able to advise further. In the case of Leigh’s disease, where a mutation has been identified in the affected child, prenatal diagnosis will usually be possible with planned help from specialist centres.

What if I am already pregnant?

There is no easy way during pregnancy to assess how severely the baby will be affected for most mitochondrial diseases (see above).

What can I do to help myself (my child)?

A good diet, including adequate vitamin intake and the avoidance of obesity are important. Since fasting increases demand on mitochondria, regular meals with, if possible, a high proportion of carbohydrate is recommended. Excessive exertion should be avoided. What level of physical activity you take will depend on how severely your muscle is affected, but for those able to exercise, this will improve well being and in some cases lead to improved muscle function. Our Regional Care Advisers can provide practical support and information. They also help families liaise between the various professionals e.g. physiotherapists, occupational therapists, social workers and teachers.

Minicore (multicore) myopathy

2010-02-07T09:00:00.000-08:00

Minicore myopathy, also called, multicore myopathy and multiminicore myopathy, falls under the umbrella of congenital myopathies. These are a group of conditions characterised by muscle weakness and wasting.
Minicore myopathy is a rare condition, and is so named because of the presence of core structures in the muscle fibres. There are four subgroups of minicore myopathy, each with varying symptoms and severity. There is currently no cure for minicore myopathy, but management of the condition is very important and includes physiotherapy, ventilation and corrective surgery where appropriate.
Minicore myopathy is sometimes called multicore myopathy, or multiminicore myopathy, and may also be abbreviated to MmD.

What causes minicore myopathy?

Minicore myopathy is often inherited in an autosomal recessive pattern. This means that both parents must carry the genetic error for their child to be affected, although neither parent is affected. Both males and females can be affected. Around half of cases of minicore myopathy are caused by a genetic error in one of two genes- Selenoprotein N1 (SEPN1) and Ryanodine receptor 1 (RYR1).
SEPN1. Errors in this gene account for around 30% of all cases of minicore myopathy. The gene is located on chromosome 1 and produces a protein called Selenoprotein N1. This gene is also associated with rigid spine muscular dystrophy, and it is now believed that the severe form of classic minicore myopathy and rigid spine muscular dystrophy are the same condition. RYR1. Some of the non-classic forms of minicore myopathy are associated with errors in the RYR1 gene. This gene is located on chromosome 19 and produces a protein which functions as a calcium channel in muscle. Errors in this gene are also associated with central core disease and a condition called malignant hyperthermia (MH). Core structures are also often seen in the muscle of people with central core disease. An overlap of the pathological appearance of what are two genetically distinct conditions may complicate the diagnosis. People with an error in the RYR1 gene, may also be susceptible to the condition malignant hyperthermia. This is an acute reaction to certain anaesthetics or muscle relaxants used for general anaesthesia. Symptoms of MH include high fever, muscle rigidity, dark brown colouration of urine and acute renal failure. MH is potentially fatal if not treated immediately with dantrolene, but can be prevented by avoiding the triggering agents. This should be brought to the attention of the consultant if surgery is to be considered.
Often cases are sporadic, with no previous family history, and the exact cause of the condition is not known.
More information on genetic inheritance is available in the factsheet ‘Inheritance and the muscular dystrophies’.

What are the common features?

There are four subgroups of minicore myopathy.
Classic form. This form accounts for around 75% of cases of minicore myopathy. Onset is usually at birth or within the first few months, and presents with floppiness (hypotonia) and delay in achieving motor milestones. Sometimes young infants can have problems with feeding and a feeding tube may be required. Most children are able to walk independently by 28 months. There is generalised weakness, although weakness of the muscles around the trunk and neck are more severe, and curvature of the spine (scoliosis) is common. There are often problems with the respiratory muscles, causing difficulties with breathing.
Progressive form with hand involvement. This form affects less than 10% of cases of minicore myopathy. It is less severe than the classic form and scoliosis and respiratory problems are mild or absent. The characteristic feature is that people with this form are doublejointed (hyperlaxity).
Antenatal form with arthrogryposis multiplex congenita (AMC). This form also affects less than 10% of people with minicore myopathy. The general feature is the presence of tightened joints (contractures) at birth, due to poor foetal movement. This form is also associated with a range of physical features including long head, low set ears, and a short neck. The respiratory muscles can be moderately to severely affected, thus problems with breathing are common Ophthalmoplegic form. The main characteristic of this form is external ophthalmoplegia. This is a condition which results in weakness of the muscles around the eye. This can lead to problems with eye movement and sometimes droopiness of the eyelids (ptosis). Along with the weakness around the eyes, there is weakness of the muscles closest to the trunk of the body.

How is it diagnosed?

Muscle biopsy. This is done in one of two ways: either a small piece of muscle is taken under general anaesthetic or a needle biopsy is performed to remove a small sample. The sample will be analysed under a microscope.
Muscle tissue from a person with minicore will have a characteristic pattern. Normal muscle tissue has two different types of fibre; type 1 and type 2. Muscle from people with minicore myopathy has more type 1 fibres than type 2. Also, within these fibres, there are structures which are called ‘cores’; which can be seen under the microscope. These structures are not specific to minicore myopathy, and so the clinical signs must be considered together with the muscle sample to give a diagnosis of minicore myopathy. A fact sheet on Muscle biopsies is available from the Information and Support Line.
Molecular testing is currently not available for minicore myopathy. It may be available for families where the specific genetic error has been identified, but a genetic testing centre would have to advise whether this was possible.

What other tests are available?

Since genetic testing is not available for this condition, prenatal diagnosis is also not available. In families where the error has been identified, both prenatal diagnosis and carrier testing may be possible, but a genetic testing centre would have to advise whether this was the case.

How will it progress?

Progression in minicore myopathy is very variable between individuals. In some people the condition remains static, whilst in others muscle weakness may worsen with time. Sometimes, individuals with the classic form of minicore myopathy may have progressive scoliosis and may show a decline in respiratory function. In most of these cases the course becomes stable in late childhood and many people continue to walk into adulthood, despite scoliosis and the requirement for respiratory support through ventilation.

Is there a treatment?

Currently there is no treatment for minicore myopathy although management of the condition is
very important.
Physiotherapy. The primary aim of an individual with a neuromuscular disorder is to increase or at least maintain function and mobility. Physiotherapy can assist in doing this, and it can also maintain breathing capacity, delay the onset of curvature of the spine (scoliosis), and help prevent the development of contractures. It is important that the physiotherapist involved is familiar with the treatment of people with neuromuscular disorders.
Exercise. There is debate over whether people with neuromuscular disorders should undertake strenuous physical exercise. Some say that putting additional strain on already weakened muscles will cause additional harm, whilst others believe that the exercise may increase muscle strength. Insufficient evidence exists to support either, but it is believed that moderate nonweight bearing exercise such as swimming, walking or peddling may be the best solution. This sort of aerobic exercise helps to maintain a healthy cardiovascular system and a steady weight.
It is however, important that this is discussed fully with a clinician. Ventilation. Breathing problems are common with minicore myopathy, and thus respiratory function should be regularly monitored. A decrease in oxygen intake can lead to, among other things, headaches, breathlessness, poor appetite and disturbed sleep. Night time ventilation involves the use of a face mask attached to a small machine, which assists in breathing. This aids the muscles which control breathing, and allows a greater intake of oxygen. Night time ventilation may be beneficial to people with minicore myopathy, but this should be discussed fully with a consultant to determine whether it is appropriate. If there is a tendency to chest infections it is worth considering pneumovax and the flu vaccine.
Corrective surgery. Scoliosis, or curvature of the spine, is common with minicore myopathy. Spinal surgery aims to correct the posture by realigning the spinal column, and involves the insertion of rods, screws or wires. There are benefits and risks associated with this surgery, and more information is available from the Information and Support Line. As with other treatments, it is very important that the options are discussed fully with a consultant or specialist, before a decision is made. In young children a spinal brace may be used and in children who do not walk moulded seating is used.
Feeding tube (or gastrostomy). This is a tube that goes into the stomach through the stomach wall and enables a person to be given food and fluids by passing them directly into the stomach via the tube. People with a myopathy may have problems with swallowing which can lead to choking and inhalation of food. This can result in chest infections. A feeding tube prevents this from happening. There are a number of different types of feeding tube which are available, and these are fitted by a short surgical procedure. A fact sheet on Gastrostomy is available from the Information and Support Line.

Is there a cure?

Currently there is no cure for minicore myopathy although much research is currently being conducted into all the congenital myopathies. Although there is no effective treatment to halt the progression, there are a couple of different ways in which to manage the symptoms of minicore myopathy and these are outlined above.

What research is currently being done?

Researchers world-wide are exploring many avenues in an attempt to develop more effective treatments and hopefully a cure. The research department at the Muscular Dystrophy Campaign, regularly monitors research advances in congenital myopathies, and produces releases which are sent to members when significant scientific advances occur. Email: research@muscular-dystrophy.org

Planning for the future?

Since the progression of minicore myopathy is very variable, planning for the future may be
difficult. Depending on the severity of the condition there are things which may have to be
considered, such as:
• Education
• Holidays
• Ventilation
• Transport
• Home adaptations
Further information on these subjects can be obtained from the Information and Support Line.
Other things to consider
Anaesthetics and muscle relaxants. As mentioned, there is an association between minicore myopathy caused by RYR1 mutations and a condition called malignant hyperthermia, which is triggered by the administration of anaesthetics and muscle relaxants. It is important that this is brought to the attention of the consultant and the anaesthetist if surgery is being considered. Medical alert card. It is very important that health professionals are aware of your condition should you require treatment. There are often issues they will have to consider. Many companies are able to provide a Medic Alert Card, which can be carried to advice of any medical condition. These come in the form of bracelets, pendants etc and carry essential information.

MDC1A (merosin-deficient congenital muscular dystrophy)

2010-02-07T08:55:00.000-08:00

What is merosin-deficient congenital muscular dystrophy?

The congenital muscular dystrophies are a group of conditions which share early presentation and a similar appearance of the muscle. Congenital means ‘from birth’ and in congenital muscular dystrophy the initial symptoms are present at birth or in the first few months. Congenital muscular dystrophies are a very heterogeneous group of conditions and in the last few years a lot of effort has gone into identifying the separate entities and in locating the gene responsible for a number of these forms.
The gene responsible for merosin-deficient congenital muscular dystrophy was the first gene to be identified in a proportion of patients with congenital muscular dystrophy and lies on chromosome 6 (1p35-p36). This gene is responsible for the production of laminin α2 which contributes to the protein called merosin.

Which are the first signs?

Babies with merosin-deficient congenital muscular dystrophy often have hypotonia (decreased muscle tone, floppiness), and may have reduced movements and contractures (tightness) in the hips, knees and elbows. Sometimes the first signs are only noted after a few months when the children have difficulties in holding their head or have a delay in learning new skills such as sitting unaided, crawling or walking.

Is merosin-deficient congenital muscular dystrophy inherited?

Yes. The pattern of inheritance is known as ‘autosomal recessive’. This means that both parents
are carriers of the condition (although clinically unaffected) and they have risk of 25%, or 1 in 4,
in each pregnancy of passing the condition on to their children.

How is merosin-deficient congenital muscular dystrophy diagnosed?

The diagnosis of merosin-deficient congenital muscular dystrophy is usually suspected from the history and examination. The specific diagnosis however is generally made by looking at a piece of muscle (muscle biopsy). Before doing a muscle biopsy (which involves taking out a small piece of muscle, usually from the thigh) a few other tests may be done.
One of these tests is a blood test which measures the level of a muscle enzyme (creatine kinase or CK) that is generally very much raised (more than 10 times the normal values).

Muscle biopsy can provide a precise diagnosis in two ways:

• When the muscle is studied under the microscope, it is possible to look for signs which might indicate a muscle problem. In children with a muscular dystrophy the muscle fibres, instead of being evenly sized, show a great variation and some of these fibres are replaced by fat and fibrous tissue.
• It is also possible to look at the presence of merosin in the muscle under the microscope. There are specific ‘tags’ which can interact with merosin and detect whether this protein is normally present or reduced. A reduction in merosin in a patient with evocative clinical features strongly suggests the possibility of MDC1A.
In MDC1A a skin biopsy rather than a muscle biopsy may also be used. This followed the discovery that the protein merosin, normally present in both skin and muscle, is absent in both tissues in patients with MDC1. A skin biopsy means only having to remove a very small skin sample from the patient and may be done under a local anaesthetic. However in most instances a muscle biopsy is preferred as it allows the study of many more proteins and therefore diagnose forms in which merosin is normal.
The following illustration shows where merosin is present in muscle:
In the upper part of the illustration, a number of relevant extracellular proteins and their interactions are shown. Laminin 2 interacts, among other proteins, with dystrolgycan. Dystroglycan is in turn associated, intracellularly, with the protein dystrophin. Genetic tests looking for abnormalities in the gene responsible for MDC1A congenital muscular dystrophy are now available in a NSCAG laboratory and provide the ultimate diagnosis. Prenatal diagnosis is a development in the diagnosis of inherited conditions. It is based on the
ability to detect the abnormality in the developing fetus. In families who have a child with MDC1
congenital muscular dystrophy who decide to have another baby it is possible to detect whether
the baby has the same protein or gene defect early in pregnancy.

Is there a treatment or cure?

At the moment there is no cure for congenital muscular dystrophy, but there are ways, described below, of helping to alleviate the effects of the condition.

Can a child with MDC1A learn to walk?

The severity of this condition varies. Children in whom merosin is completely absent or is only present in very small traces generally never achieve walking without support. Some of them may be able to stand or to walk using assistance such as long leg callipers. Some children might have a partial reduction of merosin and a proportion of the effects are milder and they may learn to walk although this may be delayed. Children who have successfully walked may lose the ability later on because as they grow older and heavier, the muscles are unable to cope with a greater strain. On the other hand it is also possible for some of these patients to retain the ability to walk for the entire life.

What other physical effects might MDC1A have on a child?

As the muscles are weak and mobility is limited, the child may develop or be born with ‘contractures’. This means that the muscle tendons tighten up and the child is unable to move the limbs or the joints as freely as a healthy child. Physiotherapy can help prevent this and a programme of exercises should be worked out with a physiotherapist very soon after diagnosis. Even a very young baby can be helped to maintain suppleness. Hips are commonly affectedand if they are dislocated this may require treatment with a splint or sometimes surgery. Most of the children with MDC1A also develop a curvature of the spine (scoliosis), this can be helped by promoting appropriate sitting support and, if required, a brace. All children with merosin deficient congenital muscular dystrophy also have a particular constitution of the white matter of the brain that can be seen following a brain scan. This is not associated with any particular problem in these children and is therefore not a worrying feature, but its presence is often searched for to confirm the diagnosis. Only a minority of children with merosin deficient congenital muscular dystrophy have seizures. These are usually well controlled with drugs, if present.

Is MDC1A progressive and is it life threatening?

Motor function remains relatively stable but when children reach puberty, and grow taller and heavier, children might experience additional difficulties.
A very common problem in patients with MDC1A is weakness of the respiratory muscles, giving rise to frequent chest infections and hypoventilation (poor breathing) at night. Both are potentially serious complications that need to be promptly recognised and acted upon. It is therefore very important to monitor respiratory function during the night by checking oxygen levels on a regular basis, usually once a year. This test is very simple and consists of applying a small wrapping around one finger. The wrapping is connected to a small machine recording the level of oxygen throughout the night. Night time breathing problems may happen in children of any age and when present, children feel tired, often have headaches in the morning, soon after they wake up, may feel sleepy during the day and lose some weight. If these signs are present or if the level of oxygen recorded at night are not satisfactory, children can be helped by referring them to a respiratory physician who will provide a mean of supporting breathing at night (ventilator). This usually requires a special facial or nasal mask attached to a small machine that pumps air when it is needed.
Another frequent problem after the first few years is failure to thrive and it is therefore also important to monitor weight and height to be sure that these children receive enough food and energy. Very often there are also problems in swallowing as the muscles which are responsible for swallowing are weak. In several cases feeding supplements are needed. Sometimes a small surgical procedure called gastrostomy can be performed to help the child to receive the appropriate level of feeding via a tube directly into the stomach and maintain his/her weight.

McArdle’s disease

2010-02-07T08:50:00.000-08:00

What is McArdle’s disease?

McArdle’s disease is a metabolic muscle disorder first described in 1951 by Dr Brian McArdle. The disorder is also called Glycogen Storage Disease Type V (GSD V). People born with McArdle’s disease are unable to produce an enzyme called muscle phosphorylase. This enzyme is important in producing the fuel source required by the skeletal muscles for exercise.
What are the symptoms?
People with McArdle’s disease develop severe muscle pain and fatigue in the first few minutes of exercise. If exercise is continued despite the pain, a severe muscle spasm or contracture will develop. This results in muscle damage leading to myoglobinuria, a dark discolouration of the urine.
Many people with the condition remember painful symptoms from early childhood but the disorder is rarely diagnosed before adulthood. Some people notice a worsening of their symptoms in middle-age and this may be accompanied by some muscle wasting, especially over the shoulders and back. Most people live normal lives and learn to improve their exercise tolerance using a “second wind”.

What is a second wind?

There are two types of exercise: aerobic exercise includes walking, gentle swimming, jogging and cycling. Anaerobic exercise is more intense or sustained exercise and includes running, walking uphill and carrying loads. The first few minutes of any exercise are usually anaerobic. Normally, during anaerobic exercise, muscle phosphorylase converts glycogen (stored starch) to glucose (sugar). The glucose enters a metabolic pathway known as the glycolytic pathway,which ultimately produces ATP (energy). During aerobic exercise, the main energy source comes from free fatty acids carried in the blood stream. These fatty acids enter a different metabolic pathway, called oxidative phosphorylation, which takes place in the mitochondria (these are the power houses of the cell) the end result is the production of ATP (energy A second wind is like a key opening the door, enabling exercise without pain for people with McArdle’s disease. After a few minutes of exercise when pain occurs, if the individual rests for a moment or two, exercise can be continued without severe pain. The second wind probably results from a switch in metabolic pathway from the glycolytic pathway to oxidative phosphorylation.

Which muscles are affected?

Any skeletal muscle is affected. Usually walking brings on symptoms in the legs and carrying heavy shopping affects the arms. Sawing, digging or squatting may affect the back muscles and some people develop pain eating chewy foods.

How is McArdle’s disease diagnosed?

A blood test will usually reveal a raised muscle enzyme known as creatine kinase (CK). Sometimes a forearm lactate test is performed, although this is not essential. The diagnosis is confirmed by a muscle biopsy, which shows an excess of glycogen and absence of the muscle enzyme phosphorylase. In up to 85% of patients from Northern Europe, an abnormality in the gene encoding for muscle phosphorylase, called R50X (previously known as R49X), can be detected on a DNA test (blood test). In practice such testing is rarely helpful and not always available and is not essential to make the diagnosis.

Is there any treatment?

The ability to develop a second wind is greatly increased by keeping physically fit. Taking regular gentle aerobic exercise, such as walking is important. At the start of exercise, when pain occurs, slow right down or stop until the pain has subsided, then try again. Sustained or severe exercise, such as weight lifting, or sprinting, must be avoided because of the high risk of muscle damage. Continuing to exercise in the presence of severe pain will also result in muscle damage and myoglobinuria, which will in turn increase the risk of acute renal failure.
Many different diets and supplements have been tested in McArdle’s disease such as high protein diet, vitamin B6 and creatine supplements, as yet there is insufficient evidence to suggest that any of these benefit people with McArdle’s disease. There is some evidence to suggest that a sugary drink prior to planned exercise might help. This however, needs to be balanced against excessive weight gain, which should be avoided at all cost. Carrying increased weight will lower your body’s aerobic threshold and make exercise more difficult. Keeping aerobically fit is the best way to condition McArdle’s muscles to improve performance and improve quality of life.

What happens if myoglobinuria occurs?

Most people with McArdle’s disease will develop myoglobinuria at some time in their lives. Myoglobinuria is a dark discolouration of the urine from a red- brown colour (mild) to a brownblack colour (severe). This is a warning sign for acute renal failure, which can occur if severe muscle damage has occurred. If this happens the kidneys stop producing urine because the draining tubules become blocked with the products of muscle breakdown.
If the episode of pain and contracture was not too severe myoglobinuria will be transient and lighter in colour. After more severe episodes the muscles may be swollen and tender and there may be flu like symptoms. Minor symptoms are managed by increasing fluid intake to maintain a good urine output. More severe episodes will require an admission to hospital for intravenous fluids and if kidney failure occurs, a period of dialysis may be required. Kidney failure is almost always reversible, but expert treatment is required immediately to prevent complications during the acute stage. It is, therefore, very important to seek medical help early should any of these symptoms occur.

Are there any other precautions?

There is a reported risk of acute muscle damage, with certain general anaesthetics (usually muscle relaxants and inhaled anaesthetics), although in practice problems appear to be very rare. The anaesthetist should be made aware of the diagnosis of McArdle’s disease, and may choose to avoid certain anaesthetic agents. Tourniquets should not be used during operative procedures in patients with McArdle’s disease.
Affected women do not seem to be disadvantaged by pregnancy or childbirth. A natural childbirth is a realistic possibility for women with McArdle’s disease.

Will I become disabled?

McArdle’s disease does not affect life expectancy. Some people do notice a slow deterioration in their symptoms over many years but by far the majority of people remain independent and able to walk.

Can it be passed on to my children?

The condition is caused by a recessive gene. This means that one abnormal copy of the gene is passed from each parent to the affected child, who in turn will have inherited two abnormal copies of the gene. The risk for both carrier parents to have an affected child is 1:4 for each pregnancy.
People who have McArdle’s disease do not usually pass the condition onto their own children because one normal copy of the gene will have been provided by their partner. However, all of their children will be carriers. Generally speaking carriers do not have symptoms.

The limb-girdle muscular dystrophies (LGMDs)

2010-02-07T08:28:00.000-08:00

This factsheet is for people for whom a diagnosis of limb-girdle muscular dystrophy (LGMD) has been suggested. This is a complicated subject since there are many different types of limbgirdle muscular dystrophy. Not all of the things that we talk about in this fact sheet will be relevant to everybody with the diagnosis.

What is limb-girdle muscular dystrophy?

Muscular Dystrophy is the name given to a group of inherited conditions where there is a progressive wasting and weakening of muscle. There are many different types of muscular dystrophy. One of the ways in which the different types of muscular dystrophy are distinguished
is by noting the groups of muscle that are involved first. The limb-girdle group of muscular dystrophies is so called because generally they cause weakness in the shoulder and pelvic girdle for example the big muscles around the top (proximal) part of arms and legs (hip, thigh and shoulder muscles). Usually weakness of the legs is noticed before that of the arms and usually the muscle of the face are unaffected.
Specialised tests for LGMD are now available through a national scheme for specialised diagnosis, the National Commissioning Group (NCG). Further information can be found at the end of this factsheet.

What are the common features?

LGMD are rare conditions and they present differently in many people, even within the same family, with regard to age of onset, areas of muscle weakness, heart and respiratory involvement, rate of progression and severity.
The different types of LGMD may have different features associated with them and some of these are described in the table below. However, the common features to all people in this group will be weakness of the big muscles of the legs and/or arms. This may result in frequent falls, difficulty in running, climbing stairs and rising from the floor. As the condition progresses, people can have problems with walking and may need to use a wheelchair over time. The involvement of shoulder and arm muscles can lead to difficulty in raising arms over head and in lifting objects. In some types of LGMD, the heart and breathing muscles may be involved.
Consequently regular checks of heart and breathing function may be needed in order to identify any changes and treat them as necessary.

What causes it?

There are many different genetic faults associated with LGMD and these are listed in the table below. These genes contain the necessary information to make muscles function. When a person has faults in a LGMD gene, the muscles can not work properly and weakness occurs. Quite often complex tests may be needed to work out the causes of LGMD in an individual person, which may include examination of a muscle biopsy and a blood sample for DNA testing.

What are the different types of limb-girdle muscular dystrophy?

The different types of LGMD have all gone through various name changes and reclassifications over the last few years. They are listed in the table below. All forms of LGMD have a genetic basis.
The LGMDs are divided into two main groups depending on the way they are passed on in families. On this basis, they are grouped into autosomal recessive or type 2 LGMD and the much rarer group of autosomal dominant or type 1 LGMD. They can now be further subdivided on the basis of the faulty gene or the muscle protein deficiency which may tell us exactly where the problem lies.

Names Inheritance
Protein involved
Clinical features
CK level
Genetic test available
LGMD2A
Calpainopathy
Calpain3
deficiency
AR Calpain3 - A common form of LGMD worldwide
- Onset of muscle symptoms: 8-15 yrs though may be earlier or later
- Weakness and wasting in the hip, thigh and shoulder muscles
- Not usually very rapidly progressive
- Joint contractures may be present
- Heart and breathing involvement is not a common feature of the condition.
Elevated Yes
LGMD2B
Dysferlinopathy
Dysferlin
deficiency
Miyoshi
myopathy
AR Dysferlin - Onset of muscle symptoms: 20 yrs though may be earlier or later - Same people with a typical hip and shoulder muscle weakness (LGMD2B); other people with difficulty standing on toes and hand weakness (Miyoshi myopathy or distal myopathy)
- Usually slow progression
- Muscle pain and swelling in calves can be present
- Heart and breathing involvement is not a common feature of the condition.
Markedly
elevated
Yes
LGMD2C, 2D,
2E, 2F
Sarcoglycanopathies
Sarcoglycans
deficiency
AR One of the
sarcoglycan
proteins
( )
- Onset of muscle symptoms: usually in childhood
- Weakness and wasting in the hip, thigh and shoulder muscles
- Rate of progression of the condition is extremely variable
- Joint contractures may be present
- Heart and breathing muscles may be involved
Elevated Yes
LGMD2G AR Telethonin So far only reported in Brazil Elevated No
LGMD2H AR TRIM32 So far only reported in Canada Elevated No
Names Inheritance Protein
involved
Clinical features CK level Genetic
test
available
LGMD2I AR FKRP
(Fukutin
related
protein)
- A common form of LGMD in the UK
and in the North of Europe
- Onset of muscle symptoms: 10-20
yrs though may be earlier or later
(with a range from 2 to 40 yrs)
- Rate of progression of the condition
is extremely variable
- Joint contractures may be present
- Heart and breathing muscles may be
involved
Elevated Yes
LGMD2J AR Titin So far only reported in Finland
- People with one copy of the faulty
gene have a distal muscle myopathy
Elevated No
LGMD2K AR POMT1 - Onset of muscle symptoms:
childhood
- Weakness and wasting in the hip,
thigh and shoulder muscles
- Severe learning difficulties
- The gene is also involved in a severe
congenital muscular dystrophy
- Few cases described
Elevated Yes
LGMD2L
AR Fukutin - Onset of muscle symptoms:
childhood
- Weakness and wasting in the hip,
thigh and shoulder muscles
- The gene is also involved in a severe
congenital muscular dystrophy
- Few cases described
- Deterioration of weakness with viral
infections
- Heart and breathing muscles may be
involved
Elevated Yes
LGMD2M AR Not known - Onset of muscle symptoms: 10-50
years
- Weakness in the hip, thigh and
shoulder muscles
- Asymmetric wasting of leg muscle
(quadriceps femoralis)
Elevated Yes
LGMD2N AR POMT2 - Recently described
- Faults in this gene are responsible
for a wide spectrum of symptoms,
ranging from severe muscle
weakness and wasting, learning
difficulties and eye problems at birth
to a milder form of LGMD
Elevated Yes
LGMD1A AD Myotilin So far described only in two families
- Faults in this gene also cause
another autosomal dominant
muscular disease, called Myofibrillar
myopathy,
- Onset of muscle symptoms:
adulthood
- Some affected individuals can have a
particular nasal pattern of speech
(dysartria)
- Heart and breathing muscles may be
involved
Normal or
mildly
elevated
Yes
Names Inheritance Protein
involved
Clinical features CK level Genetic
test
available
LGMD1B AD Lamin A/C - Faults in this gene also cause AD
Emery-Dreifuss muscular dystrophy,
peripheral neuropathy and an
unusual condition called
lipodystrophy.
- Onset of muscle symptoms: 5-20
years
- Usually slow progression
- Heart involvement is frequent and
can be the only manifestation of the
muscular condition
- Breathing problems are not common
Normal or
mildly
elevated
Yes
LGMD1C AD Caveolin3 - Onset of muscle symptoms: from
childhood to adult life
- People can present weakness and
wasting in the hip, thigh and shoulder
muscles (LGMD), a distal muscle
weakness and “rippling muscle
disease”
- Cramps and muscle pain after
exercise are common
- Usually slow progression
- Heart and breathing involvement is
not a common feature of the disease
Mildly
elevated
Yes
LGMD1D, 1E, 1F AD Not known - Very rarely reported so far Normal or
mildly
elevated
No
How is limb-girdle muscular dystrophy diagnosed?
The first clue towards the diagnosis of LGMD is usually obtained when your doctor takes your
medical history and examines you. The patient’s family history can help to identify the pattern of
inheritance and to distinguish between autosomal dominant and autosomal recessive forms.
A physical examination, particularly a neurological evaluation including a muscle strength
assessment, can help the doctor determine the pattern of the muscle involvement. Occasionally
this may suggest a particular form of muscular dystrophy but usually a number of different tests
will be needed to make the diagnosis. These may include a selection of blood tests, electrical
tests, radiological investigations and very importantly a muscle biopsy.
Blood tests can show raised creatine kinase (CK) levels which suggest there may be a problem
in the muscles. CK is a muscle enzyme, which is released into the bloodstream at high levels
when there is muscle fibre damage. In addition to elevated CK serum levels, some people often
have elevated transaminates levels. These enzymes are also referred to as liver enzymes and
people with muscular dystrophy can therefore, sometimes, be wrongly diagnosed as having liver
disease.
Electromyography (or EMG) is a test that measures the muscle’s response to stimulation of its
nerve supply and the electrical activity in the muscle. Electromyography and radiological
investigations (MRI scan) can help to identify the pattern of the muscle involvement which may
suggest a particular form of muscular dystrophy.
Each of the tests on their own can indicate that LGMD may be a likely diagnosis. It is, however,
usually by studying a muscle biopsy that we can be most clear about what type of LGMD
someone might have. This is because we are now able to look directly at the proteins which
may be reduced or absent in different types of LGMD. In most situations the muscle biopsy
gives the best chance of reaching a precise diagnosis. However, even today the muscle biopsy
alone is sometimes not enough to distinguish between the exact types of LGMD and therefore
genetic tests may be needed to confirm or identify a precise diagnosis.
In approximately 25% of all LGMD patients, a precise diagnosis can not be found in spite of all
testing which is available.
What does the muscle biopsy show?
A muscle biopsy is a surgical procedure in which a small sample of muscle is removed from
your leg or your arm and examined under a microscope. Healthy muscle has a characteristic
appearance, and is made up of closely packed fibres which are more or less evenly sized. The
muscle biopsy of a person affected by LGMD shows a loss and change of size to some of these
muscle fibres and some are even substituted with fat.
In other tests (immunochemistry (A), immunoblotting (B)), we are able to look directly at the
muscle proteins which may be reduced or absent in different types of LGMD. This can lead to
confirmation of a precise diagnosis.
A)
Dystrophic LGMD2B LGMD1C
Dysferlin Caveolin
Normal Normal Normal
B)
How has our understanding of the limb-girdle muscular dystrophies improved?
Our understanding of the LGMDs has improved dramatically over the last few years. When the
term “limb-girdle” muscular dystrophy was first coined by Dr Walton and Dr Nattrass in 1954
there was no clear understanding of what the condition really involved. It was something of a
“catch all” term used fairly widely to distinguish people with predominant limb-girdle weakness
from other types of muscular dystrophy, such as Becker, Duchenne, facioscapulohumeral and
congenital. Because this was not a very specific use of the term, a lot of people who were
thought initially to have had LGMD in fact turned out to have other conditions. On the other
hand, the diagnosis of LGMD has been delayed in other people. This was partly because there
are many other conditions that can cause weakness of the big muscle of the arms and legs.
Research over the last few years has changed things very dramatically. We can now
understand the real cause for a number of different types of limb-girdle muscular dystrophy and
can even distinguish different types. By studying the muscle biopsy, we can identify many of the
proteins which are absent in muscle and are the causes of the different types of LGMD. We also
know the genes responsible for these conditions which are now available by genetic tests. This
leads us to have greater understanding about the progression of the condition, the prominent
muscle involvement and the complications more frequently associated with the different types.
What other tests are available?
Once the exact subtype of LGMD has been defined, it may be possible to offer other testing
such as prenatal diagnosis or carrier testing for other family members. This is so variable from
condition to condition and family to family that you will need to explore this with your consultant
or ask for referral to a geneticist to discuss in more details.
What are the genetic implications?
Approximately 90% of LGMD is inherited as an autosomal recessive disorder. For someone to
have one of these conditions they have to have two faulty copies of the gene responsible. All of
our genes come in pairs, one from our mother and one from our father. If someone has an
autosomal recessive type of LGMD both of their parents must be carriers (see diagram). These
parents will, together, have a 1 in 4 chance of having another baby with LGMD.
People with autosomal recessive types of LGMD rarely have affected children (for the risk of
meeting and having a child by a carrier of the same faulty gene will be rare); all of their children
will have inherited one copy of the faulty gene but are unaffected.
The remaining subtypes of LGMD show what is known as autosomal dominant in inheritance.
This means that the condition can be passed on from parent to child (of either sex). However, it
is important to note that we are increasingly recognising that autosomal dominant conditions
can arise as a result of a so-called new fault in the gene (a “new mutation”) meaning that
someone can have an autosomal dominant condition without either parent being affected. For
the affected person, there is a 50-50 chance that their children could also be affected.
How will it progress?
All types of LGMD tend to get worse with time, but this is highly variable from condition to
condition and from person to person. It is best to discuss this with your consultant to be sure the
information is relevant to your specific case.
Is there a treatment?
There are at this stage no specific treatments or cure for the muscle weakness that arises in
LGMD, though clinical trials of experimental treatments are being planned. At present these are
not available for patients. Your consultant and the Muscular Dystrophy Campaign can give you
up to date and scientific information about clinical trials and potential suitable treatments for
patients. However, that is not to say that this means that there is nothing that can be done for
people with LGMD.
One very important reason for knowing exactly which type of LGMD someone has is to make
sure that people are getting the right follow up and management.
Maintaining good mobility is important for all patients affected by muscular dystrophy. There are
not any guidelines about the type or intensity of activities however it is recommended that any
exercise undertaken is done within a person’s limitation and remains comfortable. Extreme
tiredness, muscle pain and cramps during or after activities can mean that a person has pushed
himself too hard and therefore should be avoided. Swimming is a good activity because it
promotes movement of all muscles without increased strain.
Access to physiotherapy may be very important to keep people mobile and to keep joints
supple.
Watching out for breathing problems may lead to treatments that can be life saving and the
same is true for proper follow up of the heart. Prematurely identification of any breathing and
heart problems is important in order to promptly start proper treatments. It is very important that
all patients have access to this kind of regular follow up.
What financial help is available to people with neuromuscular conditions?
Depending on the degree of disability, some people may be entitled to social services benefits,
which may include Disability Living Allowance (DLA), Independent Living Fund (ILF), Direct
Payments and Home Adaptation Grants. These benefits can be accessed by contacting your
local social services department (asking for an assessment of need), Citizens Advice Bureau
(CAB), GP, primary health care team and/or Job Centre.
What is the National Commissioning Group (NCG)?
NCG is commissioned by the NHS and offers a diagnostic and advisory service to all patients in
the UK with Limb Girdle Muscular Dystrophy (LGMD). This service is based at the Institute of
Human Genetics in Newcastle upon Tyne. If patients wish to have this specialist assessment,
they need to be referred via their GP or consultant. The service is available at no cost to the
referring doctor.
Other relevant factsheets from the Muscular Dystrophy Campaign
LGMB1B
LGMB1C
LGMB2A
LGMB2B

Whilst every reasonable effort is made to ensure that the information in this document is complete, correct and upto- date, this cannot be guaranteed and the Muscular Dystrophy Campaign shall not be liable whatsoever for any damages incurred as a result of its use. The Muscular Dystrophy Campaign does not necessarily endorse the services provided by the organisations listed in our factsheets.

Limb-girdle muscular dystrophy 2I (LGMD 2I)

2010-02-07T08:17:00.000-08:00

LGMD 2I

LGMD 2I is an autosomal recessive form of limb-girdle muscular dystrophy (LGMD). It is one of the most common forms of LGMD, especially in Northern Europe. The age of onset of muscle weakness is extremely variable; the most common being between 10 and 20 years of age. It can also range between 2 to 40 years.

What causes it?

LGMD 2I is caused by faults in the Fukutin Related Protein gene (FKRP), which gives instructions to produce a protein important to the muscle fibres. Faults in the Fukutin Related Protein gene (FKRP) cause limb-girdle muscular dystrophy type 2I (LGMD2I), as well as a form of severe congenital muscular dystrophy (MDC1C).

How is it diagnosed?

The diagnosis can be suspected by findings on a muscle biopsy or when a doctor experienced in muscular dystrophy examines you. A serum creatine kinase (CK) blood test may also show raised levels which indicate a problem in the muscles. The diagnosis has to be confirmed by identifying the faulty gene (Fukutin Related Protein gene) which is done on a DNA sample from a blood test. This is often done following a clue from the muscle biopsy or examination.

What symptoms are common?

People with LGMD2I often have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. This weakness is usually even on both sides of the body and leg involvement is present before shoulder and arms. This weakness can result in frequent falls, toe walking or in a particular walking with “waddling gait” (swaying from side to side). This
can also cause people to have hyperlordosis (arched back). People can have difficulty in running, climbing stairs and rising from the floor. As the condition progresses, mobility becomes increasingly more difficult.
Shoulder and arm weakness can lead to difficulties in raising the arms over the head and in lifting objects. Some people may complain of muscle pain and cramps, especially in the legs, even before the onset of muscle weakness.
Calf hypertrophy (large calves) and macroglossia (large tongue) can be present. People with LGMD2I can develop joint contractures (tightening) and more frequently they involve the ankles. Facial and neck muscles are not usually involved and therefore swallowing problems are unlikely. Unlike congenital muscular dystrophy type 1C, learning difficulties and eye problems are not features of LGMD type 2I.
People with LGMD2I are at risk of heart and breathing problems. These problems can occur even when weakness is mild. However, as the condition progresses, heart and breathing involvement tend to increase. People with heart problems can experience symptoms of breathlessness and tiredness. However, some people can have heart problems even when they do not show symptoms. Breathing problems are common in LGMD2I and these may occur before loss of ambulation.
The first symptoms of breathing involvement can include; poor sleep, nightmares, tiredness or headaches after waking up in the morning, lack of appetite and falling asleep during the day. As LGMD2I can involve the diaphragm, the first symptoms may be difficulty in breathing when lying flat.

What are the implications of the diagnosis?

Inheritance

LGMD2I is an autosomal recessive condition caused by changes in a gene. People affected with this condition have 2 faulty copies of the Fukutin Related Protein gene; one inherited from each parent. This means that both parents must be carriers but remain healthy.
The exact frequency of the Fukutin Related Protein gene faults in the population is not known but there is a particular fault which tends to recur relatively frequently, especially in the North European populations. Genetic carrier testing is available for this common fault, because the risk of meeting and having a child by a carrier of this common faulty gene is slightly increased. However we can not rule out that a person could carry a different fault in the same gene in which case, there is no genetic carrier testing available because the risk of meeting and having a child by such a carrier would be very unlikely.
To summarise, carrier testing is only available for the common fault for LGMD2I. Carrier testing of the whole gene is available only when the risks are increased due to intra-familial marriage. Children of people affected with LGMD2I will have inherited one faulty copy of the Fukutin Related Protein gene and therefore will all be carriers but are unaffected.

Progression and complications

LGMD2I is quite a variable condition in terms of severity. The weakness is always progressive with time although the rate of progression varies from person to person. Same people may be only mildly affected, where as others may show a relatively rapid deterioration of weakness, resulting in loss of independent ambulation in early adulthood.
Life expectancy and quality of life depends upon the identification and treatment of the associated complications such as heart and breathing problems.

Treatment and management

So far there are no specific treatments for LGMD2I, however managing the symptoms of the condition improves a person’s quality of life. Keeping mobile is important for all people affected with muscular dystrophy. There are not any guidelines about the type or intensity of activities however it is recommended that any exercise undertaken is done within a person’s limitation and remains comfortable. Extreme tiredness, muscle pain and cramps during or after activities can mean that a person has pushed himself too hard and therefore should be avoided.
Swimming is a good activity because it promotes movement of all muscles without increased strain.
Joint contractures (tightening) can occur in LGMD2I and therefore regular physiotherapy is recommended. This can be carried out by a physiotherapist or people can be taught to do this by themselves in their own home. These types of exercises can include the stretching of all joints; in particular, the ankles, knees and elbows. If ankle contractures impair mobility, referral for an orthopaedic opinion may be indicated. Orthoses (splints) are sometimes worn day or
night to enhance good positioning of the ankle joints. In the case of severe contractures, minor
surgical procedures may be necessary.
People with LGMD2I are at risk of developing breathing difficulties. Therefore regular monitoring of respiratory function (FVC), in lying as well as sitting, is recommended in order to identify any problems and treat them if necessary. Sometimes overnight studies are indicated (Pulse Oximetry) and people may benefit from treatment with assisted ventilation at night. Pneumovax vaccination and annual flu immunisation should be performed in people affected by LGMD2I in order to prevent serious chest infections.
Because of the risk of problems with the heart in LGMD2I, regular heart checks are required and these should include ECG and Echocardiogram. Many treatments are available and these will be discussed with you by a cardiologist if necessary.

Sarcoglycanopathies: LGMD2C, LGMD2D, LGMD2E and LGMD2F

2010-02-06T04:26:00.000-08:00

LGMD2C (γ-sarcoglycan deficiency); LGMD2D (α-sarcoglycan deficiency); LGMD2E (β- sarcoglycan deficiency); LGMD2F (δ-sarcoglycan deficiency) are also known as sarcoglycanopathies. LGMD2C, 2D, 2E and 2F are autosomal recessive forms of limb-girdle muscular dystrophy (LGMD). The age of onset of muscle weakness is variable but most commonly is in childhood. Onset can also occur in early adulthood. These forms of LGMD were previously called “autosomal recessive muscular dystrophy on childhood”.

What causes it?

Sarcoglycanophies are a group of limb-girdle muscular dystrophies (LGMD) caused by faults in one of the 4 genes which give instructions to produce 4 proteins (sarcoglycans) important to the muscle fibres. Each type of sarcoglycanopathy is genetically different but people have similar symptoms.

How is it diagnosed?

The diagnosis can be suspected by findings on a muscle biopsy or when a doctor experienced in muscular dystrophy examines you. A serum creatine kinase (CK) blood test may also show raised levels which indicate a problem in the muscles.
The muscle biopsy usually shows a deficiency of the involved proteins and can be helpful to identify the specific gene responsible of the symptoms.
The diagnosis has to be confirmed by identifying the faulty gene (α-SG-, β-SG, γ-SG-, δ-SG gene) which is done on a DNA sample from a blood test.
Because sarcoglycan genes are large genes and sometimes genetic analysis of all 4 genes is necessary, testing is very lengthy and results may not be available for many months.

What symptoms are common?

People with Sarcoglycanopathy often have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. This weakness is usually even on both sides of the body. Leg weakness can result in frequent falls, toe walking or in a particular walking with “waddling gait” (swaying from side to side). This can also cause people to have hyperlordosis (arched back) and scoliosis (curved spine). People can have difficulty in running, climbing stairs and rising from the floor. As the condition progresses, mobility becomes increasingly more difficult.
Shoulder and arm weakness can lead to difficulties in raising the arms over the head and in lifting objects and shoulder blade winging may be present (scapular winging). Some people may complain of muscle pain and cramps, especially in the legs. Calf hypertrophy (large calves) and macroglossia (large tongue) can be present. People with sarcoglycanopathies can develop joint contractures (tightening) and more frequently they involve the ankles.
Facial and neck muscles are not usually involved and therefore swallowing problems are unlikely.
People with sarcoglycanopathy are at risk of heart and breathing problems. These problems can occur even when weakness is mild. However, as the condition progresses, heart and breathing involvement tend to increase.
Heart involvement is more frequent in people affected by LGMD2E (β-sarcoglycanopathy), while LGMD2D is rarely associated with heart problems.
People with heart problems can experience symptoms of breathlessness and tiredness. However, some people can have heart problems even when they do not show symptoms. Breathing problems are common in sarcoglycanopathies, but this is usually after loss of ambulation. The first symptoms of breathing involvement can include; poor sleep, nightmares, tiredness or headaches after waking up in the morning, lack of appetite and falling asleep during the day.

What are the implications of the diagnosis?

Inheritance
Sarcoglycanopathies are autosomal recessive conditions caused by changes in a gene. People affected with these conditions have 2 faulty copies of one of sarcoglycan genes, one inherited from each parent. This means that both parents must be carriers but remain healthy. The exact frequency of sarcoglycan gene faults in the population is not known but they are rare conditions. Therefore, people with Sarcoglycanopathy rarely have affected children (for the risk of meeting and having a child by a carrier of the same faulty gene will be very unlikely unless you have a partner to whom you are related). Children of people affected with sarcoglycanopathy will have inherited one faulty copy of one of the sarcoglycan genes and therefore will all be carriers but are unaffected.
Consequently, carrier testing is not generally available unless the risks are increased due to intra-familial marriage.

Progression and complications

Sarcoglycanopthies are quite variable conditions in terms of severity. The weakness is always progressive with time although the rate of progression varies from person to person. Many people show a relatively rapid deterioration of weakness, resulting in loss of ambulation in early adulthood. Consequently, wheelchair use may be required with progression of the condition. LGMD2D usually is milder than LGMD2E and 2C.
Life expectancy is into adulthood and depends upon the identification and treatment of the associated involvement of the heart and the breathing muscles. Treatment and management So far there are no specific treatments for sarcoglycanopathies, however managing the symptoms of the condition improves a person’s quality of life.
Keeping mobile is important for all people affected with muscular dystrophy. There are not any guidelines about the type or intensity of activities however it is recommended that any exercise undertaken is done within a person’s limitation and remains comfortable. Extreme tiredness, muscle pain and cramps during or after activities can mean that a person has pushed himself too hard and therefore should be avoided. Swimming is a good activity because it promotes movement of all muscles without increased strain.
Joint contractures (tightening) can occur in sarcoglycanopathies and therefore regular physiotherapy is recommended. This can be carried out by a physiotherapist or people can be taught to do this by themselves in their own home. These types of exercises can include the stretching of all joints; in particular, the ankles, knees and elbows. If ankle contractures impair mobility, referral for an orthopaedic opinion may be indicated. Orthoses (splints) are sometimes
worn day or night to enhance good positioning of the ankle joints. In the case of severe contractures, minor surgical procedures may be necessary.
People with sarcoglycanopathies are at risk of developing breathing difficulties. Therefore regular monitoring of respiratory function (FVC) is recommended in order to prematurely identify any problems and treat them if necessary. Sometimes overnight studies are indicated (Pulse Oximetry) and people may benefit from treatment with assisted ventilation at night.
Pneumovax vaccination and annual flu immunisation should be performed in people affected by sarcoglycanopathies in order to prevent serious chest infections.
Because of the risk of problems with the heart in sarcoglycanopathies, regular heart checks are required and these should include ECG and Echocardiogram. Many treatments are available and these will be discussed with you by a cardiologist if necessary.

Limb-girdle muscular dystrophy 2B (LGMD 2B)

2010-02-06T04:16:00.000-08:00

LGMD 2B (also known as Dysferlinopathy)

LGMD 2B is an autosomal recessive form of limb-girdle muscular dystrophy (LGMD). The age of onset of muscle weakness is extremely variable; the most common being between 20 and 30 years.

What causes it?

LGMD 2B is caused by faults in the dysferlin gene, which contain instructions to produce a protein important to the muscle fibres. Faults in the dysferlin gene can also cause another condition, called Miyoshi myopathy which predominantly shows symptoms of distal weakness, especially involving the calf muscles in the lower limbs.

How is it diagnosed?

The diagnosis can be suspected by findings on a muscle biopsy or when a doctor experienced in muscular dystrophy examines you. A serum creatine kinase (CK) blood test may also show raised levels (up to 200 fold of the normal range) which indicate a problem in the muscles. The diagnosis has to be confirmed by identifying the faulty gene (dysferlin gene) which is done on a DNA sample from a blood test. This is often done following a clue from the muscle biopsy or examination. Because this is a very large gene, testing is very lengthy and results may not be available for many months.

What symptoms are common?

People with LGMD2B often have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. Calf muscle wasting is also a predominant feature in the majority of people, and they may complain of difficulties in standing on their tiptoes. The weakness can be more severe on one side of the body and leg involvement is present before shoulder and arms. This can result in frequent falls, difficulty in running, climbing stairs and rising from the floor. As the condition progresses, people can have problems with walking.
The distal muscles (hand and forearm muscles in upper limbs and ankle and calf muscles in the lower limbs) can also be involved and occasionally people affected by LGMD2B show both thigh and foot weakness. It is worth mentioning, however, that these symptoms can also be present in some people at the onset of the condition. When this distal muscle involvement is present, people may have difficulties in walking because of foot drop which causes them to stumble frequently. Shoulder and arm weakness can lead to difficulties in raising the arms over the head and in lifting objects. Some people complain of muscle pain and swelling in the legs, especially in the calves, but this is usually transient.
Facial and neck muscles are not usually involved and therefore swallowing problems are unlikely.
Whether heart problems are present in LGMD2B is under debate at the moment. Clinically significant heart problems appear to be rare.
Patients with LGMD2B are at risk of developing respiratory muscle weakness and experience breathing difficulties with the progression of the condition, but this is usually a late complication.

What are the implications of the diagnosis?

Inheritance
LGMD2B is an autosomal recessive condition caused by a change in a gene. People affected with this condition have 2 faulty copies of the dysferlin gene; one inherited from each parent. This means that both parents must be carriers but remain healthy.
The exact frequency of dysferlin gene faults in the population is not known but it is a rare condition. Therefore, people with LGMD2B rarely have affected children (for the risk of meeting and having a child by a carrier of the same faulty gene will be very unlikely unless you have a partner to whom you are related). Children of people affected with LGMD2B will have inheritedone faulty copy of the dysferlin gene and therefore will all be carriers but are unaffected.
Consequently, carrier testing is not generally available unless the risks are increased due to intra-familial marriage.

Progression and complications

LGMD2B is quite a variable condition in terms of severity and the weakness is always progressive with time although the rate of progression varies from person to person. The rate of
progression is usually slow and most people remain ambulant.
Life expectancy is generally within a normal range because the heart and breathing muscles are usually not affected. In later stages of the condition, breathing difficulties can occur but are usually less severe than in other muscular dystrophies. These symptoms can include; poor sleep, nightmares, tiredness or headaches after waking up in the morning, lack of appetite and falling asleep during the day.

Treatment and management

So far there are no specific treatments for LGMD2B, however managing the symptoms of the condition improves a person’s quality of life.
Keeping mobile is important for all people affected with muscular dystrophy. There are not any guidelines about the type or intensity of activities however it is recommended that any exercise undertaken is done within a person’s limitation and remains comfortable. Extreme tiredness, muscle pain and cramps during or after activities can mean that a person has pushed himself too hard and therefore should be avoided. Swimming is a good activity because it promotes movement of all muscles without increased strain.
Joint contractures (tightening) are not a frequent feature in LGMD2B however they can occur as
consequence of poor mobility. Therefore regular physiotherapy is recommended. This can be carried out by a physiotherapist or people can be taught to do this by themselves in their own home. These types of exercises can include the stretching of all joints; in particular, the ankles.
Foot drop can occur in Miyoshi myopathy and less frequently in LGMD2B. An orthopaedic opinion may be indicated and orthoses are sometimes worn to help with this problem.
Breathing problems are uncommon in LGMD2B. However with progression of the muscle weakness, people with LGMD2B are at risk of developing mild breathing difficulties. Therefore regular monitoring of respiratory function (FVC) is recommended. Sometimes overnight studies are indicated (Pulse Oximetry).
Regular cardiac assessment is usually not required because to date there is no clear evidenceof heart muscle involvement in this condition.

Limb-girdle muscular dystrophy 2A (LGMD 2A)

2010-02-06T04:05:00.000-08:00

LGMD 2A ( also known as Calpainopathy)
LGMD 2A is an autosomal recessive form of limb-girdle muscular dystrophy (LGMD). It is one of
the most common forms of LGMD. The age of onset of muscle weakness is extremely variable; the most common being between 8 and 15 yrs, though it can range between 2 to 50 years.

What causes it?

LGMD 2A is caused by faults in the calpain 3 gene, which gives instructions to produce a protein important to the muscle fibres.

How is it diagnosed?

The diagnosis can be suspected by findings on a muscle biopsy or when a doctor experienced in muscular dystrophy examines you. A serum creatine kinase (CK) blood test may also show raised levels which indicate a problem in the muscles. The diagnosis has to be confirmed by identifying the faulty gene (Calpain 3 gene) which is done on a DNA sample from a blood test. This is often done following a clue from the muscle biopsy or examination.

What symptoms are common?

People with LGMD2A often have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. This weakness is usually even on both sides of the body and leg involvement is present before shoulder and arms. This can result in frequent falls,
difficulty in running, climbing stairs and rising from the floor. As the condition progresses, people
can have problems with walking.
Shoulder and arm weakness can lead to difficulties in raising the arms over the head and shoulder blade winging may be present (scapular winging). Some people complain of muscle pain, especially in the legs. Joint contractures (tightening) may be present and more frequently involve the ankles. Facial and neck muscles are not usually involved and therefore swallowing problems are unlikely.
Heart problems are not reported in this condition. Patients with LGMD2A are at risk of developing respiratory muscle weakness and experience breathing difficulties with the progression of the condition, but this is usually a very late complication.

What are the implications of the diagnosis?

Inheritance
LGMD2A is an autosomal recessive condition caused by a change in a gene. People affected with this condition have 2 faulty copies of the Calpain 3 gene; one inherited from each parent. This means that both parents must be carriers but remain healthy.
The exact frequency of Calpain 3 gene faults in the population is not known but it is a rare condition. Therefore, people with LGMD2A rarely have affected children (for the risk of meeting and having a child by a carrier of the same faulty gene will be very unlikely unless you have a partner to whom you are related). Children of people affected with LGMD2A will have inherited one faulty copy of the Calpain 3 gene and therefore will all be carriers but are unaffected.
Consequently, carrier testing is not generally available unless the risks are increased due to intra-familial marriage.

Progression and complications
LGMD2A is quite a variable condition in terms of severity and the weakness is always progressive with time although the rate of progression varies from person to person. The course of the condition can be mild and wheelchair use may be required many years after onset. Life expectancy is generally within a normal range because the heart and breathing muscles are usually not affected. In later stages of the condition, breathing difficulties can occur but are usually less severe than in other muscular dystrophies. These symptoms can include; poor sleep, nightmares, tiredness or headaches after waking up in the morning, lack of appetite and falling asleep during the day.

Treatment and management

So far there are no specific treatments for LGMD2A, however managing the symptoms of the condition improves a person’s quality of life.
Keeping mobile is important for all people affected with muscular dystrophy. There are not any guidelines about the type or intensity of activities however it is recommended that any exercise undertaken is done within a person’s limitation and remains comfortable. Extreme tiredness, muscle pain and cramps during or after activities can mean that a person has pushed himself too hard and therefore should be avoided. Swimming is a good activity because it promotes movement of all muscles without increased strain.
Joint contractures (tightening) can occur in LGMD2A and therefore regular physiotherapy is recommended. This can be carried out by a physiotherapist or people can be taught to do this by themselves in their own home. These types of exercises can include the stretching of all joints; in particular, the ankles, knees and elbows. If ankle contractures impair mobility, referral for an orthopaedic opinion may be indicated. Orthoses (splints) are sometimes worn day or night to enhance good positioning of the ankle joints. In the case of severe contractures, minor surgical procedures may be necessary.
With progression of the muscle weakness, people with LGMD2A are at risk of developing breathing difficulties. Therefore regular monitoring of respiratory function (FVC) is recommended. Sometimes overnight studies are indicated (Pulse Oximetry). Regular cardiac assessment is usually not required because there is no involvement of the heart muscle in this condition.

Limb-girdle muscular dystrophy 1C (LGMD 1C)

2010-02-06T04:00:00.000-08:00

LGMD 1C (also known as Caveolinopathy).

LGMD 1C is an autosomal dominant form of limb-girdle muscular dystrophy (LGMD). The age of
onset of muscle weakness is variable and ranging from childhood to adulthood.

What causes it?

LGMD 1C is caused by a fault in the Caveolin3 gene, which gives instructions to produce a protein important to the muscle fibres. People with faults in the caveolin-3 gene can present with
a broad spectrum of symptoms, which are classified as limb-girdle muscular dystrophy (LGMD1C), distal myopathy or Rippling muscle disease.

How is it diagnosed?

The diagnosis can be suspected by findings on a muscle biopsy or when a doctor experienced in muscular dystrophy examines you. A serum creatine kinase (CK) blood test is often mildly elevated, but in a few cases, CK elevation may be much more marked. Some people may not have any weakness and show only raised serum CK levels. The diagnosis has to be confirmed by identifying the faulty gene (caveolin3) which is done on a DNA sample from a blood test. This is often done following a clue from the muscle biopsy or examination.

What symptoms are common?

LGMD1C is a rare disease and so far only few families affected by this muscular dystrophy have been reported. Because of this, the range of weakness and the progression of the condition of people with caveolin-3 deficiency are not well known.
People with LGMD1C can have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. Other people can show predominant distal muscle weakness (hand and forearm muscles in upper limbs and ankle and calf muscles in the lower limbs). This weakness is even on both sides of the body and usually is mild to moderate. Upper leg weakness can result in frequent falls, difficulty in running, climbing stairs and rising from the floor. As the condition progresses, people can have problems with walking. Shoulder and arm weakness can lead to difficulties in raising the arms over the head and in lifting objects. When distal muscle involvement is present, people may have difficulties in walking because of foot weakness (foot drop) which causes them to stumble frequently. People who have hand weakness may find difficulties in simple tasks (for example opening bottles).
Rippling muscle disease is a condition in which people have visible ripples which move over the muscle. These can occur spontaneously or be induced by rapid tapping of the muscles. Many people affected by caveolinopathy, regardless of their symptoms, may show muscle rippling at the onset or later stages of the condition.
It is important to mention that the individual features of muscle weakness can be different from person to person, even in the same family.
Muscle hypertrophy (large muscles), especially calf hypertrophy, is often present in people with LGMD1C. Often people complain of muscle pain and cramps, especially in the legs and after exercise. Facial and neck muscles are not usually involved and therefore swallowing problems are unlikely.
Heart and breathing problems are usually not a feature in this condition. However, heart involvement with dilated cardiomyopathy has been rarely reported.

What are the implications of the diagnosis?

Inheritance
LGMD1C is an autosomal dominant condition caused by a change in a gene. People affected with this condition have 1 faulty copy of the Caveolin3 gene inherited from one parent. This means that usually the parent who carries the same faulty gene is also affected but may not be aware of this because their symptoms may be very mild. However, the change in the caveolin3 gene could have begun for the first time (“new fault” or “new mutation”). People affected by LGMD1C have 50-50 chance of passing on the faulty gene and the condition to their children (of either sex). Prenatal diagnostic testing is available and this can be discussed with your consultant or geneticist in more detail.

Progression and complications
LGMD1C is quite a variable condition in terms of severity and the weakness, but usually the progression is slow to moderate and people remain ambulant.
Life expectancy is generally within a normal range because the heart and breathing muscles are usually not affected.

Treatment and management
So far there are no specific treatments for LGMD1C; however managing the symptoms of the condition improves a person’s quality of life. Keeping mobile is important for all people affected with muscular dystrophy. There are not any guidelines about the type or intensity of activities however it is recommended that any exercise undertaken is done within a person’s limitation and remains comfortable. Extreme tiredness, muscle pain and cramps during or after activities can mean that a person has pushed himself too hard and therefore should be avoided.
Swimming is a good activity because it promotes movement of all muscles without increased strain.
Although joint contractures are not a frequent feature of Caveolinopathy, they can occur as consequence of poor mobility. Regular physiotherapy can be useful to maintain good joint mobility. This can be carried out by a physiotherapist or people can be taught to do this by themselves in their own home.
Problems with breathing are usually not associated with LGMD1C, but many clinics obtain regular breathing assessment (FVC) as part of regular follow up.
Regular cardiac assessment is usually not required because there is not strong evidence of heart muscle involvement in this condition. However, this can be discussed with your consultant on an individual basis.
Other relevant factsheets from the Muscular Dystrophy Campaign The Limb Girdle Muscular Dystrophies (LGMD)

Limb-girdle muscular dystrophy 1B (LGMD 1B)

2010-02-05T13:14:00.000-08:00

LGMD 1B (also known as Laminopathy)

LGMD 1B is an autosomal dominant form of limb-girdle muscular dystrophy (LGMD). The age of on set of muscle weakness is variable; the most common presentation is before 20 years, however some people may present with symptoms when they are older.

What causes it?

LGMD 1B is caused by a fault in the Lamin A/C gene, which gives instructions to produce a protein important to the muscle fibres. Faults in the Lamin A/C gene also cause autosomal dominant Emery-Dreifuss muscular dystrophy, an isolated cardiomyopathy, an autosomal recessive peripheral neuropathy (Charcot–Marie–Tooth disorder type 2B1) and an unusual condition called Lipodystrophy.

How is it diagnosed?

The diagnosis can be suspected by findings on a muscle biopsy or when a doctor experienced in muscular dystrophy examines you. A serum creatine kinase (CK) blood test is often within the normal range or mildly elevated.
Unusually, in a few cases, CK elevation may be much more marked. The diagnosis has to be confirmed by identifying the faulty gene (Lamin A/C gene) which is done on a DNA sample from a blood test. This is often done following a clue from the muscle biopsy or examination.

What symptoms are common?

People with LGMD1B often have initial symptoms of weakness and wasting (loss of muscle bulk) in the hip, thigh and shoulder muscles. This weakness is usually even on both sides of the body and leg involvement is present before shoulder and arms. This can result in frequent falls, difficulty in running, climbing stairs and rising from the floor. As the condition progresses, people
can have problems with walking. Shoulder and arm weakness can lead to difficulties in raising the arms over the head and shoulder blade winging may be present (scapular winging).
As the condition progresses, the distal muscles (hand and forearm muscles in upper limbs and ankle and calf muscles in the lower limbs) can also be involved. People may experience difficulty in doing simple tasks due to hand weakness (for example opening bottles) and in walking due to foot weakness (foot drop) which causes them to stumble frequently.
Some people complain of muscle pain, especially in the legs. Less often, calf hypertrophy (large calves) may be present. As the condition progresses, people may develop joint contractures (tightening) in the arms (elbows) and legs (ankles). Facial and neck muscles are not usually involved. However some people may show mild facial weakness, with difficulties in inflating their cheeks, whistling and experience fatigue in chewing.
People with LGMD1B are at risk of heart problems. These heart problems can be mild to severe even when weakness is not impacting on a person’s daily activities. Problems with the heart can begin at the onset of weakness and tend to increase with time.
The heart involvement in LGMD1B usually consists of rhythm and conduction disturbances and less frequently dilated cardiomyopathy. People with heart problems can experience symptoms of breathlessness, tiredness or palpitation (funny beats). However, some people can have heart problems even when they do not show symptoms.
Less frequently, people with LGMD1B may develop respiratory muscle weakness and experience breathing difficulties with the progression of the condition. Breathing symptoms can include; poor sleep, nightmares, tiredness or headaches after waking up in the morning, lack of appetite and falling asleep during the day.

What are the implications of the diagnosis?

Inheritance

LGMD1B is an autosomal dominant condition caused by a change in a gene. People affected with this condition have 1 faulty copy of the Lamin A/C gene inherited from one parent. This means that usually the parent who carries the same faulty gene is also affected but may not be aware of this because their symptoms may be very mild. However, the change in the Lamin A/C gene could have begun for the first time (“new fault” or “new mutation”).
People affected by LGMD1B have 50-50 chance of passing on the faulty gene and the condition to their children (of either sex). Prenatal diagnostic testing is available and this can be discussed with your consultant or geneticist in more detail.

Progression and complications

LGMD1B is quite a variable condition in terms of severity and the weakness, but usually the progression is slow to moderate and people remain ambulant.
Life expectancy depends upon the identification and treatment of the associated involvement of
the heart and the breathing muscles.

Treatment and management

So far there are no specific treatments for LGMD1B, however managing the symptoms of the condition improves a person’s quality of life. Keeping mobile is important for all people affected with muscular dystrophy. There are not any guidelines about the type or intensity of activities, however it is recommended that advice on exercise should be discussed with your consultant because of the associated heart problems.
Joint contractures (tightening) or foot drop can occur in LGMD1B and therefore regular physiotherapy is recommended. This can be carried out by a physiotherapist or people can be taught to do this by themselves in their own home. An orthopaedic opinion may be indicated and orthoses (splints) are sometimes worn to enhance good positioning of the ankle joints or help with foot drop if there is weakness in the feet.
Because of the risk of problems with the heart inLGMD1B, regular heart checks are required and these should include ECG and Echocardiogram. Many treatments are available and affected people are likely to need the insertion of a device (defibrillator) which controls the heart rate. This will be discussed with you by a cardiologist.

With progression of the muscle weakness, people with LGMD1B may develop breathing difficulties. Therefore, regular monitoring of respiratory function (FVC) is recommended. Sometimes overnight studies are indicated (Pulse Oximetry). Other relevant factsheets from the Muscular Dystrophy Campaign: The Limb Girdle Muscular Dystrophies (LGMD)

Facioscapulohumeral muscular dystrophy

2010-02-05T12:42:00.000-08:00

What is it?

It is a muscle wasting condition, caused by a genetic fault, which may be affecting the regulation
of the level of many of the different proteins in muscles.

Why this name, and are there others?

The name describes the usual distribution of weakened muscles: ‘facio’=facial; scapulo’=shoulder blade; ‘humeral’= upper arm. Landouzy-Dejerine and facioscapuloperoneal muscular dystrophy are two previously used terms. Also, some people with a diagnosis of scapulohumeral or scapuloperoneal syndromes may have this condition. However, the legs can also be affected.

How rare is it?

It is probably the third most common muscular dystrophy (after Duchenne and myotonic dystrophies), although its frequency may vary in different places and quite possibly in different racial groups. Estimates of frequency have varied from one in about 400,000 to one in 20,000.
In Britain, the frequency is at least one person in every 50,000, and probably closer to one in 20,000, accounting for between about 1200 and 3000 cases in all.

What causes it?

It is a genetic condition, present from when or soon after egg and sperm come together at conception. Normally, at a particular site on the gene map, each of us has many copies of a particular sequence of genetic instruction (DNA), arranged like a train of identical carriages. FSHD is caused when the number of copies is reduced below a certain level, like a train having too few carriages. In some way this seems to influence the production or assembly of several of the protein components of the affected muscles.

How severe or mild is it?

The degree of weakness or disability can vary quite widely between different affected members in a family, but can show even greater variation between people in different families. For some, it can result in weakness not only of facial muscles and shoulders/upper arms, but also of additional combinations from the neck, forearms, wrists, fingers, hips, legs, ankles and the back muscles. Around 10-20% of people eventually require a wheelchair, but by contrast, up to one third remain unaware of symptoms at least into old age, although may well have subtle detectable clinical signs. The majority of people come between these two extremes. The average severity of presentation in a family, or in a single case, seems to correlate with the smallness of the number of copies of the DNA repeat sequence which remain (i.e. the fewer copies left, the greater is the severity).
In general, the most severely affected people tend to be the ones who have the altered genetic instruction for the first time in the family, and where the symptoms of weakness are evident from early childhood.

Are men and women affected equally?

We now know that, on average, men do tend to show more weakness and from a slightly earlier age than women (see also question 16). The reason for this is not yet clear. Within large families, and therefore excluding the most severe cases, women are more likely to be less severely affected and so could be unaware that they have inherited the condition.

What are the mildest signs that someone is affected?

Within the context of a family history of FSHD, weakness of facial muscles can be suspected if the eyes remain slightly open when asleep, particularly in young children, or if the eyelids cannot be screwed tightly enough to bury the eyelashes. Difficulties in pursing the lips to whistle or to play a woodwind or brass instrument, or in blowing up balloons, are also suggestive of the condition. During the teenage years or in adulthood, excessive aching around the shoulders, rounded shoulders and thin upper arms may be the first presenting signs or symptoms.

Does FSHD affect lifespan?

Generally speaking, lifespan is not affected, except perhaps in the most severe cases with greatly impaired mobility and consequent greater risk of chest infections. There are some recent reports suggesting an increased association with heart rhythm disorders, but only in a few cases, and these are responsive to appropriate medication. Because of these reports, adults with FSHD would be advised to see their GP (or hospital doctor) every few years for a simple heart check.

Will I become disabled?

The earlier in life the weakness appears the greater its eventual severity. Nevertheless, the progression of either arm or leg weakness in the individual can be hard to predict. Although the legs are affected to some degree in over 50% of people, for those in whom this does not become evident until early adulthood, even an eventual requirement for a wheelchair is unlikely. To some extent, knowledge of the size of the DNA rearrangement (i.e. the number of repeat units remaining) in a person with FSHD can give a broad guide as to whether the course of the condition would be expected to be relatively mild or more severe.
One fairly common feature of FSHD is an asymmetry of weakness: an uneven distribution of muscle weakness where one side of the body is more affected than the other (particularly early on). This is often evident in the shoulders, usually with the right side to be the first one involved in right-handed people.

In what way are the legs affected?

Early weakness at the ankles causing ‘foot drop’ is not uncommon. Some degree of weakness at the knees or hips develops by middle age in over 50% of people. Together with weakness in the back muscles, this can result in a typical backward-leaning and high-stepping gait, although only 10-20% ever requires a wheelchair.

Can any other problems be anticipated?

In some of the earliest childhood onset cases, learning difficulties and epilepsy have been reported. Hearing loss and specific problems with blood vessels at the back of the eye have been found, and although this rarely causes visual problems, a periodic eye check may be useful. It is still uncertain whether these rare features are generally associated in mild degree with FSHD, or are limited to a few more severe cases.
Muscle pain is unfortunately a quite frequent complaint accompanying FSHD, often in the early stages. This may relate to inflammation within the muscles, which seems to occur more in FSHD than other muscular dystrophies. Treatment with simple analgesia combined with antiinflammatory agents is usually tried, but the effectiveness for relief can vary. Further studies are needed.

How is it inherited?

A separate gene determines each hereditary characteristic or function. These genes are packed together into chromosomes like beads on a string. There are two copies of each chromosome (excepting the X and Y chromosomes in males), and hence two copies of each gene (a pair), coming one from each parent. The ‘gene’ for FSHD is at one end of each copy of chromosome 4. In FSHD, one copy of this particular pair is faulty (part of it is missing, which is referred to as a ‘deletion’). Hence there is a 50:50 (1 in 2) chance for each of the offspring of an affected parent to inherit the faulty copy, resulting in FSHD. They also have an equal chance of inheriting the good copy (resulting in no risk for these individuals or their descendants of being affected by FSHD). This pattern of inheritance is called ‘autosomal dominant’.

With completion of the ‘human genome project’ has the gene causing FSHD been
identified?

Unfortunately the situation is a little more complex than as discussed (in answer 12.) above. Amongst genetic conditions, FSHD seems so far to be unique in that the genetic fault (‘mutation’) is the reduction (‘deletion’ at one end of chromosome 4) of multiple copies of a repeated sequence of DNA (likened to reducing the number of carriages in a train). This DNA change, which is the dominantly inherited factor, is probably exerting an effect on the way that the function of many genes is regulated in muscle, and particularly in the muscles of the face and shoulder girdle. Hence, there may be many ‘genes’ which are involved in causing FSHD, but for which the controlling dominantly inherited mutation always occurs at the same place on chromosome 4. Much current research in FSHD is aimed at trying to define this link.

Can FSHD be diagnosed from a blood sample?

The DNA mutation causing FSHD can indeed be recognised from a blood sample in most people with this condition. However, interpretation of the test is not always easy, and the DNA sample will need to be forwarded to one of a few molecular genetic laboratories able to offer this. In individual cases it can be harder to exclude the diagnosis than to confirm it, although both are usually made easier if blood samples are also taken from both parents of a possible affected person.
In families where there are several people known to be affected, confirmation of diagnosis, or genetic prediction for an individual family member, will almost always be possible if blood samples are collected from several of the affected people.

Is there always a family history?

A person diagnosed with FSHD, particularly if this is in early childhood, may have a fresh mutation (i.e. they have not inherited it from either of their parents). More often, however, a person diagnosed with FSHD will have inherited the faulty gene from one of his or her parents. It may be that a newly diagnosed person finds that there is a family history, but that this had not been recognised before because the symptoms of other family members had been very mild, or had been misdiagnosed. We now also know that in a significant proportion of even quite early onset cases in children, who appear to be the first ones in a family, one of the parents can show the same FSHD mutation in some of their cells but not in others. This ‘mosaic’ situation in the parent may not give any symptoms in them, but does mean that further children of theirs would
have a risk of being affected. We would therefore always recommend that both parents be invited to provide blood samples for DNA study if they wish to know about potential risk to future children.
In other cases genetic testing may help resolve any uncertainty over the affected status of a young adult. Family members or couples seeking further information should refer to their local Clinical Genetics Service.

How severely affected would my sons and daughters be?

The age at onset of symptoms, and hence the severity of FSHD, seems to correlate broadly with the extent of the DNA rearrangement on chromosome 4, which, once it has arisen, remains a fixed size in a family. Thus there will be some families where FSHD will always tend to be quite severe, and others where it will always be relatively mild. However, there can still be considerable variation within a family for severity and age at onset. Partly, this is due to differences between men and women. Although men and women develop the same symptoms, males tend to develop these earlier, and be more severe at a given age than females. By age 30 years, just about all males with FSHD exhibit symptoms, but only two-thirds of females do. We now know that some people (particularly men) with average or mild presentations of FSHD, may, if they are the first cases in a family, have a mixture of normal and FSHD-type cells and their offspring, who have inherited the FSHD mutation, would do so in all their cells, and therefore present earlier and more severely.
Data from many families suggests that offspring inheriting the faulty gene are likely to be affected from a similar young age and at least as severely as occurred in their affected parent, although in large families affected daughters with FSH might be milder than their fathers.

At what age does it usually start?

This is dependent on the extent of the DNA rearrangement. In large families with several affected members, an affected person usually first becomes aware of muscle weakness in teenage years or early adulthood, when he or she experiences difficulty in raising one or both arms, or notices prominent shoulder blades or wasting of upper arm muscles. In the more severe cases, which are often the first ones in a family and arising from a new mutation giving a small residual DNA repeat length, impaired movement of facial muscles, particularly around the mouth, can be evident by early childhood, followed by the shoulder girdle and upper arm weakness. In these children progressive weakness of the legs can start to develop by teenage years and lead to the need for a wheelchair.
By contrast, in the mildest families, with the largest residual DNA repeat lengths, people inheriting the condition may remain unaware of symptoms until even late in adulthood.

If I have no symptoms can I still carry the gene and pass it on to my children?

If the person with FSHD has been affected from childhood, it is very unlikely that an adult relative (say a brother or sister) who is unaware of any symptoms, could ‘carry’ the faulty gene or pass on FSHD to their children. The parents of the affected child are an exception, as they could be ‘carrying’ the mutation but in only some of their cells, and hence pass this on to more than one child.
For people from families where several relatives or a parent have FSHD, one cannot give the same level of reassurance except following DNA testing. In these situations, many people ‘at risk’ may be affected only mildly, and are unaware of the abnormal signs that are present.
Although some degree of reassurance may be possible if examined by a doctor well familiar with the condition, we now know that up to one-third of adult women carrying the milder mutations for FSHD, and a probably much smaller proportion of men, may not be showing any definite sign of the condition. Therefore, the answer to this question can only be given reliably following DNA testing.

If one of my children is affected, but another seems clear, is he or she likely to have ‘escaped’ inheriting FSHD?

If the apparently unaffected child is several years beyond the age at which the affected one first
presented with symptoms, it becomes very likely that they have not inherited the condition. This is particularly so if the affected child is the first-presenting person in the family, and if DNA
testing has shown that their condition has arisen from a new DNA rearrangement (a new mutation) not present in a DNA sample from either parent. However, if either parent is clinically affected or carries the mutation, only DNA testing can give reassurance. If a child has no signs of FSHD, requests for DNA testing would normally be refused until the child is of an age to choose this for themselves.

Can I avoid passing the faulty gene on to my children?

Accurate pre-natal testing, performed by chorion villus biopsy (CVS), usually at 11 weeks gestation, is now available to most couples who would wish this, and whose offspring would be at risk of FSHD. It is essential that genetic (DNA) tests be performed first on blood samples from the affected parent or child to define the DNA mutation in that family. Blood samples would usually be required from both parents, and in some cases from other affected relatives. The CVS procedure is now widely available, although the tissue sample obtained would be forwarded to one of a few specialist genetic laboratories. Couples considering this should consult with their local genetic service that would advise accordingly, preferably prior to becoming pregnant.

Treatment

Can I improve muscle strength?

There are no cures or specific drug treatments. Regular gentle exercise (especially swimming) is beneficial. It is essential to keep your weight down (through diet if necessary) in order to reduce stress on already weakened muscles. If exercises are undertaken to increase muscle strength any build-up should be done gradually.

Can surgery help?

The scapular muscles, which attach the shoulder blades to the chest, are often very weak and this leads to difficulty in lifting the arms. The operation of scapular fixation (fixing the shoulder blades to the ribs at the back) has enabled some people to regain more use of their arms. Because prolonged immobilisation of limbs could increase the weakness of disused muscles, combined assessment from a neurologist and an orthopaedic surgeon prior to operation is advised. For people who have troublesome inflammation of the eyes as a result of them if they are remaining open at night, surgery to bring the eyelids closer can be offered if artificial tears alone are insufficient.

Are anaesthetics a risk?

There is no known risk, but you should be sure that the anaesthetist is aware of your diagnosis
prior to operation.

Should I declare it on insurance forms?

Once the diagnosis has been made you have an obligation to declare it when requested. As there is no significant effect on life span, you should ask your doctor for a letter of support if you run into problems. When applying for a driving licence, especially HGV or PSV, this may be issued for a limited duration, with renewal subject to satisfactory medical examination.
The FSH Support Group offers support and encouragement to families and individuals that have FSHD.

Duchenne muscular dystrophy

2010-02-04T13:56:00.000-08:00

Some questions answered for parents who have just learned about the diagnosis.

What is Duchenne muscular dystrophy?

It is one of more than 20 types of muscular dystrophy. All the muscular dystrophies are caused
by faults in genes (the units of inheritance that parents pass on to their children) and they cause
progressive muscle weakness because muscle cells break down and are gradually lost. The Duchenne type affects only boys (with extremely rare exceptions) and a problem in this gene is known to result in a defect in a single important protein in muscle fibres called dystrophin. It is named after Dr Duchenne de Boulogne who worked in Paris in the mid-19th century who was one of the first people to study the muscular dystrophies.

How serious is it?

This is a very serious condition. Most affected boys develop the first signs of difficulty in walking
at the age of 1 to 3 years and are usually unable to run or jump like their peers, they often struggle to climb stairs and need to use a banister for support. Rising from the floor can also prove difficult.
As the condition progresses boys with DMD are unable to walk as far or as fast as other children and may occasionally fall down. Some boys also have learning and or behavioural difficulties, which may begin to manifest at this stage.
By about 8 to 11 years (rarely earlier or a little later) boys become unable to walk and by their late teens or twenties the condition is severe enough to shorten life expectancy. There are however many forms of management which are now available, which have changed the outlook and which we believe in most cases can help with the complications of the condition.

How common is it?

About 100 boys with Duchenne muscular dystrophy are born in the United Kingdom each year. There are about 1500 known boys with the disorder living in the UK at any one time. For the general population the risk of having an affected child is about 1 in every 3500 male births.

Is there any treatment?

Unfortunately no cure has yet been discovered. We do have ways to manage the condition, which help with its complications. These have had a very important impact on the quality and length of life that can be expected with this condition. A great deal can be done to help limit the effects of the muscular dystrophy and this includes treatments which are now definitely known to help some of the problems which may be life threatening, but no treatment is known which affects the actual loss of muscle cells. Intensive research to find a cure is carrying on in many centres around the world. You can find updates on progress in this area in the MDC magazine Target md and on the MDC website.

How is Duchenne muscular dystrophy diagnosed?

Reliable tests are available once somebody has recognised that a child’s problems might be due to this relatively rare condition. All affected boys have very abnormally high levels of an enzyme called creatine kinase in their blood. Most hospital laboratories can do this test. But there are other even rarer causes of a positive creatine test, so for a specific diagnosis in families with no previous affected member other tests are needed. These may involve genetic testing (looking for the actual fault in the dystrophin gene) and a muscle biopsy which can be studied to look at the dystrophin protein.

Can we be sure there is no mistake in the diagnosis?

With the most reliable genetic and protein tests, the diagnosis is very clear indeed. There are only two conditions, which are at all likely to cause any confusion in diagnosis to a doctor experienced in Duchenne dystrophy - and both of these are other types of muscular dystrophy. Autosomal recessive types are about 20 times rarer than the Duchenne type in boys and can be somewhat similar, but the specialised tests can pick out the differences.
The Becker type of muscular dystrophy is a milder variant of dystrophin deficiency but there may be some overlap in severity with the Duchenne type. It may be difficult in very young children to gauge severity at first but in the great majority of cases the position is clear. Protein and genetic tests can make this distinction clearer as well.

How is it inherited?

Duchenne muscular dystrophy is caused by an X-linked gene (that is, the gene is on the X chromosome; girls have two of these and boys only one). This means that only boys are affected but that their mothers may be carriers. Actually in almost half of all affected boys nowadays it turns out that the faulty gene has arisen by a change in the gene or ‘mutation’ in the boy himself and no other member of the family carries it. But this may be difficult to prove and can be decided only after careful and expert assessment of the family.
In just over half of all cases the mother carries the gene but is usually not herself affected by it. Such women are known as ‘carriers’. Each subsequent son of a carrier has a 50:50 chance of being affected and each daughter has a 50:50 chance of being a carrier herself. A small number of female carriers of the gene have a mild degree of muscle weakness themselves and are then known as ‘manifesting carriers’.
One of the most important things that needs to be done soon after the diagnosis of a boy with Duchenne muscular dystrophy is to seek genetic advice and appropriate tests for those members of the family who are at risk of being carriers.

How can we be sure that no other boy in the family has it?

If a boy of any age has a normal creatine kinase blood test you can be sure that he is not affected and will never develop the condition.

Can any carriers in the family be identified?

This may be less easy but geneticists can identify from the family tree which women are at risk of being carriers. A combination of creatine kinase and DNA blood tests allows the great majority of such women to be either identified as carriers or given a strong reassurance that their risk is very low. Specialised genetic advice is now available to all families.

Can DMD be diagnosed before birth?

Once a child with DMD has been born in a family, it is often possible to offer prenatal diagnosis in future pregnancies, either for the mother or for other women who are found to be at risk of being carriers. This is normally possible when DNA studies give precise information that allows the status of the foetus to be identified. This is achieved by studying the foetus's own DNA in a chorion villus biopsy. This test is performed on a tiny piece of the developing placenta usually at about the 11th-12th week of pregnancy.
Further information is available in the Organisation’s leaflet on Carrier detection and pre-natal diagnosis.

What medical help will he need now?

Very little in the early days after diagnosis. Active exercise is important but not necessarily with medical supervision though you may find it helpful to be in touch with a physiotherapist to keep an eye on things. The most important way in which a doctor can help at this stage is to help you, as parents, to learn as much as you can about Duchenne muscular dystrophy and to provide or arrange genetic advice. It should also be possible at this stage to set up an arrangement for long term follow up for continuing discussion and help.

What medical help will he need later?

Regular supervision from a clinic used to dealing with this condition will become increasingly important as the years go by. Knowing the kind of problems that can develop means that much can be done to prevent them or manage them appropriately. In the early stages, your son will be
monitored carefully for signs of increasing problems with his mobility, and in particular for the development of shortening of his muscles (contractures). Physiotherapy plays an important role
in helping here.
As getting about becomes more difficult, extra options to help will be discussed and a plan of action decided later on, attention will be paid to management of any spinal curvature and surveillance of heart and breathing muscles. Picking up problems in any of these areas means that they can be managed properly, reducing the long-term effects. Management of heart and breathing problem has improved dramatically over the last few years and this improvement is likely to continue.

What can we do to help our son?

Being a parent is a challenge even without having a child with DMD. This news will have made you revaluate some of the hopes and expectations you had for your son. The new challenge is to move forward in the light of this information, to continue to grow as a family and value each member and ensure that he or she has an equal share of family time.
Sometimes unaffected brothers and sisters miss out on the attention and affection they need because their parents are preoccupied or sad. Time devoted to them and also, to each other will make your family life a more secure and stimulating base for your son. There will not be time for
everything, and it is important to recognise that and not feel guilty, but recognising everyone’s needs - including your own - is very important for you all.
You may well feel very alone. Everyone’s experience is different, but in time you may find it helpful to speak to another family who have had a similar diagnosis. Your consultant or family care officer should be able to help with this.
There is no doubt that news like this changes a family in very fundamental ways. You are going to have to become an expert in this new and unwelcome subject to make sure you have the confidence to foresee and prevent problems through the years. However bad it seems to start with though, families do find a way to live with DMD. Your son will develop and mature and it is important that he is encouraged to achieve all the independence he possibly can.

What should I tell my children?

This is a very difficult question and one which people often worry about. As time goes by, your son, and other children if you have them, will inevitably ask questions, which you need to be prepared to answer openly and honestly as they come up. Knowing that they can ask you questions, which will be answered truthfully, will enhance your relationship. That is not to say that you need to tell them ‘everything’ at the first opportunity. Listen to what your children are asking and answer exactly that. You may find it helpful to rehearse how you will say things - people often say that this helps and the reality is then not nearly as bad as they had feared. It is also true that often your child will know more than you think. Allowing the opportunity to talk openly is very brave. It can be a lot more satisfactory in the long run than keeping up a silence wherein everyone is trying to protect each other. It is important to reassure your other children that they are not going to develop the same problem - this can sometimes be a hidden worry and that is nobody's fault.

What plans will we have to make for the future?

The previous paragraphs may give you some ideas about planning to help your son. One practical problem that needs to be planned for in advance is how he is going to get about in your house and remain as independent as possible when he can no longer climb stairs or when he uses a wheelchair.

Will he be able to go without help to the toilet or his bedroom?

Will he be able to use the bath etc? Solutions can be found to these problems but special equipment may be needed and sometimes the family home needs adaptations or even an extension.
The ideal house for a person in a wheelchair is sometimes a bungalow and you should consider whether you might try to find one, but for other people different solutions may be better. Local authority grants, building permission and the building work itself can all take an unbelievably long time to arrange and it can be a struggle to get what you want. It is vital to start thinking about these decisions in advance. It is also crucial to seek skilled advice before making an expensive decision about your home. The Muscular Dystrophy Campaigns Adaptations Manual, local social services and local Occupational Therapy (OT) services and perhaps your local Family Care Officers, may be able to help you get this advice.

What about school?

Most children with muscular dystrophy cope pretty well in their local infant’s school and in their
first few years at junior school. Talk to your school and give them as much information as you can. Your local clinic should be able to help you keep the school fully informed. If walking becomes too precarious or access to classrooms, toilets or dining room becomes too difficult some schools will make special arrangements or even structural alterations. Local authority transport to and from school can be arranged if necessary as can help in the classroom. If the school is too unsuitable an alternative mainstream school in the district or a special school will provide the answer.
Alternatively when he leaves school your son will naturally find it difficult to do a job requiring any muscle strength, and his leisure activities will be restricted in the same way. From the earliest days at school his education is therefore going to be doubly important so that his talents, whether as an artist, organiser, writer or whatever can be fully developed. Computers offer a real route to help children with DMD develop their talent to the best of their abilities. Higher or further education often offers good opportunities for school leavers.
Some boys with Duchenne muscular dystrophy are found also to have learning difficulties. This problem is rarely severe and when it does occur, unlike the muscle weakness, it never becomes worse as time goes by. In those boys who have the problem, language and communication skills are often the main difficulty. Manual skills, design sense and imaginativeness are often excellent which is perhaps why many young men with Duchenne muscular dystrophy become very good artists and model makers.
As parents you can work with the school to discover and develop your son’s best talents as well as helping him to learn to cope with tasks he finds difficult.

Congenital myasthenic syndromes (CMS)

2010-02-04T13:44:00.000-08:00

This fact sheet is for children and adults diagnosed with congenital myasthenic syndrome. It’s a complex subject, so information has been adapted to suit all audiences. Not all information will apply to every person with this condition.

What is CMS?

CMS are a group of inherited conditions which are present from birth or early childhood. Many different genetic defects in a series of different genes can cause CMS. These defects cause problems with the way the messages are transmitted from the nerves to the muscles, causing weakness (myasthenia) and the muscles tire easily (fatigue). Muscle weakness varies depending on the type of genetic defect, so impact on mobility ranges from mild to severe. In the less severe cases the condition may causes drooping eyelids and fatigue, but only mildly interferes with daily life. In the most severe cases however, where breathing or other essential bodily functions are greatly affected, CMS can be life-threatening or even fatal. Symptoms usually start in early childhood, although there are some adult onset cases, and are similar to those of myasthenia gravis but can’t be treated with the steroids and treatments which are effective on myasthenia gravis.

Is CMS the same as myasthenia gravis?

No. When most people talk about myasthenia they mean myasthenia gravis - an autoimmune condition like rheumatoid arthritis, which can affect both children and adults. Myasthenia gravis causes the body to produce proteins that block and destroy some of their receptors, making messaging from nerves to muscles less effective. Myasthenia gravis can be treated with steroids, immunosuppressive drugs and thymectomy (surgical removal of the thymus gland).

How is CMS inherited?

In the majority of cases children with CMS will inherit a faulty gene from each parent. This is called an autosomal recessive (AR) mutation. If each parent only has one copy of the faulty gene, they will not have any symptoms themselves, but there will be a 25% chance that any future pregnancy will result in a child with the condition.
Children who have inherited an AR type of CMS will pass on one copy of the faulty gene to their child but are unlikely to have affected children because the chances of their partner also carrying a faulty CMS gene are very small, unless they marry a blood relative.

Diagnosis and treatment

The type of CMS known as ‘slow channel CMS’ is known to be inherited in a different way. It is an autosomal dominant disorder which means that it can be passed on from either parent to their child. If either parent has the condition there is a 50% chance of any future pregnancy resulting in a child with CMS. In other rare cases, the foetus may develop a sudden new fault in its genetic makeup without the parents carrying any faulty genes. For further information about genetics and inheritance, please see our Inheritance and the muscular dystrophies factsheet.

How is CMS diagnosed?

A specialist needs to make a clinical diagnosis and carry out further testing for CMS, which will include taking a clinical history and tests which measure the function and response of muscles and nerves to repeated stimulation.
Further tests will also need to be carried out to exclude other causes of symptoms, including specialised genetic investigations using DNA from a blood sample and a muscle biopsy to exclude other similar neuromuscular conditions. A final definite diagnosis is made through genetic analysis of a DNA sample. Once a diagnosis of CMS is made, families should be referred to a specialist genetics centre for a full discussion of the genetic implications of the diagnosis. Prenatal
diagnosis can be offered in a future pregnancy if the genetic mutation has been identified.

What are the symptoms of CMS?

While various symptoms may need further investigation, they can vary greatly from person to person and not all symptoms will be found or experienced in the same way. The following symptoms may be noticed in someone with CMS:
In the womb: decreased movement and too much amniotic fluid (polyhydramnios). From birth: stiff joints (arthrogryposis) reduced movements, a weak suck and cry, difficulty feeding, swallowing and possibly episodic breathing difficulties. Children: may start walking late, become tired with exercise, only able to walk short distances, unable to hold their arms above the head for long, and have difficulty climbing stairs. They may also have difficulty chewing food, scoliosis (curvature of the spine) a waddling gait and a tendency to fall easily.
Sometimes there are distinctive facial features such as a prominent lower jaw, high arched palate and crowded teeth (maloclusion), droopy eyes when tired, reduced eye movement with occasional double vision and unclear or nasal speech. Children with CMS may also get frequent chest infections and need hospital treatment. Adults: may have similar problems to those of children but noticed at a later age. They are often described as poor sports people at school, easily fatigued especially on climbing stairs and have weakened ability to move their fingers and wrists. Symptoms can vary greatly from person to person and not all will be present or experienced in the same way although fatigue is a common characteristic.
Many other conditions that affect muscle, nerve and brain function can cause similar symptoms to the above.

How does CMS progress?

It is important to get a correct diagnosis to be able to predict the long term outcome. If diagnosed early, CMS can be treated and prevented, to some extent, with medication. Almost all children with CMS will be able to walk independently and it does not affect intellect in any way. Some CMS is so mild that it is only diagnosed in late childhood, adolescence or even adulthood. Supportive treatment is offered in all cases.
Breathing support, help with feeding, monitoring of lung function, physiotherapy and speech and language therapy may be needed. Most CMS patients find that their muscle strength improves with time and the need for medication reduces. In some rare cases no treatment which helps is found. Some will need life-long medication to maintain muscle strength. In some instances, although body strength improves with treatment, eyelid droop and eye movements do not.

What are the different types of CMS?

There are many types of CMS- dependent on where the problem in sending messages from the nerve to muscle occurs.(see diagram on the next page) Identifying where the problem occurs may allow drugs to be described which can help with the management of symptoms. CMS can fall into three categories:
 pre-synaptic - at the nerve ending, where there is a fault is in the production and
release of the chemical (acetylcholine) which signals to the muscle to contract
 synaptic - in the gap between the nerve and muscle, or
postsynaptic - on the muscle where there is a fault in the receptors that receive
the chemical message.
Many of the defects are known to be caused by alterations in known genes and so can be identified using a DNA test. Some people require a muscle biopsy to test how the nerve-muscle junction works. There are forms of CMS that can’t yet be identified but rapid advances in research are helping to find more of the genes responsible.
Medication, anaesthesia and operations. Some drugs such as antibiotics, cardiovascular drugs and drugs for psychiatric conditions should be avoided by people with CMS because they interfere with normal neuromuscular function and may make symptoms worse.
Always check with the doctor who treats your CMS before taking any new medication as it can be very dangerous to start a new drug without consultation. It is also very important to inform the anaesthetist and surgeon of your diagnosis before undertaking any surgery or treatment. A Medic-Alert card or bracelet is an important source of information to emergency care providers about the special situation of a person with CMS.

Exercise

It is important to try to get as much gentle exercise as possible and to continue physiotherapy which can help prevent complications like joint stiffness (contractures) However it may help to use a wheelchair for distances to help conserve strength. In the event of serious health concerns
Your GP is the first point of contact for minor illness but for more serious concerns, you should contact your physician or paediatrician and in an emergency dial 981 for an ambulance. It is advisable to keep a list of useful numbers handy for family members and carers to contact in an emergency.
If your child has CMS you should have a rapid access agreement to the paediatric service at the local hospital to avoid having to wait to be seen if he or she is unwell. People who have breathing difficulties and recurrent chest infections should be under the care of a specialist respiratory centre and will be advised to have an annual flu and pneumococcal vaccine. Parents and carers should also be trained in cardiopulmonary resuscitation. Talking to your child’s school It is a good idea to talk to your child’s school and school friends about the allowances that need to be made for their condition. For example they may not understand the additional preparations involved at home and in travelling to and from school which might mean needing to start school late and leave early.
It might also need to be explained that your child needs to use a computer or laptop rather than writing by hand, and that he or she needs extra time to complete work nd take tests. He or she should also avoid sitting on the floor and having to get up and sit down frequently. They should use a chair of appropriate height.
You will need to agree a suitable level of participation in PE and sport, with the opportunity to stay indoors during playtime if necessary. They should not be expected to raise their hand or shout aloud in the classroom. They may need extra time for eating and drinking and be able to take medication at a specific time without fail.
Children can be teased or criticised for their droopy eyes, squint, slurred speech and quiet voice and symptoms can vary from day to day and time to time. It is therefore important that they are listened to and offered appropriate support. A statement of special education needs is often needed to get extra assistance in the school or help with transport and referral to the community paediatrician and their nursing team will provide essential support

Where to go for more information

Apart from your doctor and hospital specialist there are specialist nurses in many centres who will offer help, advice and support to a family. Ask your GP or hospital specialist whether such a service exists in your area. For advice about home adaptations and local authority grants contact the occupational therapist in your local social services department. Your GP or health visitor can also refer you to the Children with Disabilities Team in your local social services department

Disclaimer

Whilst every reasonable effort is made to ensure that the information in this document is complete, correct and up-to-date, this cannot be guaranteed and the Muscular Dystrophy Campaign shall not be liable whatsoever for any damages incurred as a result of its use. The Muscular Dystrophy Campaign does not necessarily endorse the services provided by the organisations listed in our factsheets.

Congenital muscular dystrophies

2010-02-04T13:38:00.000-08:00

What is congenital muscular dystrophy?

The congenital muscular dystrophies are a group of conditions which share early presentation and a common muscle pathology. Congenital means ‘from birth’ and in the great majority of cases of congenital muscular dystrophy the initial symptoms are present at birth or in the first few months.
Babies with congenital muscular dystrophy often have hypotonia (low muscle tone or floppiness), and may have reduced movements. Other common signs are contractures (tightness) in the ankles, hips, knees and elbows. The contractures can sometimes be severe and affect several joints (known as arthrogryposis). They happen because the baby has not had the muscle strength to move freely enough in the womb. Some of these babies may also have respiratory problems because of weakness of breathing muscles.
In some children who do not have contractures the first problems are only noted after a few months because of difficulties in holding the head or delay in learning how to sit unaided, stand or walk.

How many people are affected by congenital muscular dystrophy?

A precise and recent study on the frequency of this disorder in UK is not available, but we estimate that 1 baby every 20,000-50,000 is born with congenital muscular dystrophy.

Is congenital muscular dystrophy inherited?

Yes. The pattern of inheritance is known as ‘autosomal recessive’. This means that both parents are carriers of the condition (although clinically unaffected) and they have a risk of 25%, or 1 in 4, in each pregnancy of passing the condition on to their children. Occasionally a case may be ‘sporadic’ which means is a one-off with little risk of recurrence in other children. There is no accurate way of predicting who is and who is not a carrier.

How many forms of congenital muscular dystrophy exist?

Congenital muscular dystrophy is a very heterogeneous group of conditions. These are generally grouped under two main types:

1. Children who only have muscle weakness involving all muscles but have normal intelligence
2. Children who have muscle weakness and learning difficulties, with or without seizures.

Learning difficulties may be subtle, moderate or severe. While this classification is helpful in most cases, an overlap between different categories can occur. A lot of effort has gone into identifying separate entities within each group and in locating the gene responsible for each form. A number of specific conditions can now be recognised but for others a final diagnosis is still not possible.
Genetic advances. There have been recent developments in the genetics of congenital muscular dystrophy which have resulted in a better understanding of this group of disorders. The first gene abnormality to be discovered was that of the LAMA2 (laminin alpha-2 chain) gene, the gene responsible for merosin. This form affects approximately 40% of the children with congenital muscular dystrophy. More recently several other abnormal genes have been identified and today we know nine genes responsible for separate forms of congenital muscular dystrophy, each of them with specific clinical features.
A number of cases do not have any of these forms and more research into these conditions is needed.

How is congenital muscular dystrophy diagnosed?

A baby with congenital muscular dystrophy is usually first diagnosed as a ‘floppy baby’. Doctors
can see the symptoms described above, but as these could be due to a number of different conditions, they have to conduct a series of tests to try to make an accurate diagnosis. Firstly a blood test is taken and the level of a muscle enzyme assessed (the creatine kinase or CK level). In approximately 40% of cases of congenital muscular dystrophy this level is 5-20 times higher than normal.
Muscle ultrasound may also help to detect abnormalities of the muscle. The technique is very simple, similar to the ultrasound studies carried out in pregnancy and may provide further evidence of the involvement of the muscle.
An electromyography (EMG) test may also be done. A small needle is inserted into muscle and the electric activity recorded. This test may provide evidence of an abnormal pattern of electric activity in the muscle.
At this stage however even in the cases with high CK levels, abnormal muscle ultrasound and EMG, an additional test which is required in almost every case is a muscle biopsy.
Muscle biopsy can help to identify the subtype of congenital muscular dystrophy to provide a precise diagnosis in several ways:

• When the muscle is studied under the microscope, it will show variation in the size of muscle fibres and that some of these fibres are replaced by fat and fibrous tissue.
• In addition, the production of individual components of the muscle fibre can be studied in detail with specialised tests. This greatly helps to narrow down the diagnostic possibilities. In the forms of congenital muscular dystrophy in which the gene defect has been identified, genetic tests will provide the ultimate diagnosis. Prenatal diagnosis is possible in several types of congenital muscular dystrophy. It is based on the ability to detect the genetic abnormality in the developing foetus. This however can only be used in the forms of congenital muscular dystrophy associated with a recognised gene defect or a specific protein deficiency.

Is there a treatment or cure?

At the moment there is no cure for congenital muscular dystrophy, but there are ways, described below, of helping to alleviate the effects of the condition.

Is congenital muscular dystrophy progressive and is it life threatening?

The condition is fairly stable and the child appears to gain strength as he or she gets older. In several forms therefore acquisition of new skills with time is possible although difficulties will always be present. If the condition is not progressive, it is possible to live a normal lifespan. In some conditions the muscle weakness however becomes worse with time and can lead to respiratory problems. This may happen in children of any age.

Can a child with congenital muscular dystrophy learn to walk?

The severity of this condition varies greatly from person to person. As the severity varies so much sometimes even within the same form of congenital muscular dystrophy, it is important not to assume that certain developments will or will not take place, but to work with the child to achieve the goals which are in his or her power.
Some children will walk but sometimes this can be delayed until five years of age or older. Leg splints (callipers) are often used to assist a child to walk. Children who have successfully walked may lose the ability later on because as they grow older and heavier, the muscles are unable to cope with a greater strain. Other children never achieve walking.

What other physical effects might congenital muscular dystrophy have on a child?

The presence and the severity of other problems depend on the form of congenital muscular dystrophy. Some features however are generally found in many children with congenital muscular dystrophy, irrespective of the form.
As the muscles are weak and mobility is limited, the child may develop or be born with ‘contractures’. This means that the muscle tendons tighten up and the child is unable to move the limbs or the joints as freely as a healthy child. Physiotherapy can help prevent this and a programme of exercises should be worked out with a physiotherapist very soon after diagnosis.
Even a very young baby can be helped to maintain suppleness. Hips are commonly affected and if they are dislocated this may require treatment with a splint or sometimes surgery.
Breathing and feeding problems are commonly observed in some forms of congenital muscular dystrophy but are less frequent in others. As these complications can be helped by timely recognition and professional advice and intervention, it is advisable for individuals with congenital muscular dystrophy to be regularly followed by someone with expertise in neuromuscular disorders. There are several examinations that might be needed, such as over night sleep studies to monitor the breathing quality during sleep. In some children it is also advisable to reduce the risk of chest infections, performing flu jabs and other vaccinations.

Charcot-Marie-Tooth Disease (CMT)

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Sometimes known as Hereditary Motor and Sensory neuropathy (HMSN) or Peroneal Muscular
Atrophy (PMA)

What is Charcot-Marie-Tooth disease?

Charcot-Marie-Tooth disease is named after the three neurologists who first described the condition in 1886. Many different names have been used to describe CMT but the other commonly used name is hereditary motor and sensory neuropathy (HMSN). This is an accurate term as it refers to the two primary features of this condition i.e the condition is hereditary and affects the motor and sensory peripheral nerves. CMT or HMSN therefore is used to describe a group of conditions that give rise to weakness and wasting of the muscles below the knees and often those of the hands. Many affected people also have loss of feeling in the hands and feet, and this is the ‘sensory’ component. The term neuropathy refers to the fact that it is the peripheral nerves (which connect the spinal cord to the muscles, joints and skin, carrying messages in both directions), which do not function normally. As the name implies, these are inherited disorders. CMT is also referred to as peroneal muscular atrophy, because the peroneal muscles on the outer side of the calves are particularly affected. Other names include Dejerine-Sottas disease and hereditary hypertrophic neuropathy. The term CMT is now the favoured term and is the term most commonly used in the literature.
CMT does not describe a single disorder, but a group of conditions that are superficially similar. It is important to determine exactly what kind of CMT someone has, and this can be achieved by
careful examination, taking a family history, electrical tests (nerve conduction studies), and genetic studies on blood samples. This sort of assessment also serves to distinguish CMT from other non-genetic causes of neuropathy, and this is particularly important in people who do not have affected relatives.
The different types of CMT Peripheral nerves can be thought of as being electrical cables: the fibres (like wires) run down the middle and are wrapped in insulating material (myelin).
If the myelin is damaged the nerve impulses tend to be conducted more slowly than usual. If the
fibres (also called axons) are damaged, the speed of conduction is normal but the size of the signal is reduced.
These changes can be detected by electrical tests. Traditionally, the commonest forms of CMT have been divided into two types: in type 1 the damage is to the myelin resulting in slow conduction, and this is referred to as the demyelinating type of CMT, whereas in type 2 it is the
nerve fibres that are at fault and the term axonal type CMT is used.
Although major advances have been made in the last decade in the identification of the genes responsible for CMT, not all of the genes associated with CMT have yet been identified. This means that the electrical test (nerve conduction studies) is still often very useful in making the diagnosis. An exception is when there is a clear family history of autosomal dominant inheritance
(see below), when DNA testing for the commonest form of CMT (type 1A) might be performed as a first investigation. Although the electrical tests are usually clearcut, allowing a diagnosis of CMT type 1 or CMT type 2, in some cases it may be difficult to decide from the electrical test which type of CMT a patient has and the term intermediate CMT is used. Although this can be confusing for patients it is useful for doctors in deciding which genes to screen. In the future, when all the causative genes are identified, a comprehensive classification of CMT will be available but in view of the fact that there are likely to be numerous genes involved it is probable that electrical tests will remain important in the initial assessment of patients.
Previously, the term HMSN III was applied to patients with a particularly severe form of HMSN
starting in very early life. HMSN III is also called Dejerine Sottas Disease (DSD) and Congenital
hypomyelinating neuropathy (CHN) and both these terms are commonly used clinically. HMSN III was thought to be inherited in an autosomal recessive pattern, unlike the autosomal dominant pattern of inheritance of the common types of CMT types 1 and 2 (see below). We now know that HMSN III is usually associated with a defect in the genes that cause CMT type I and that most cases are a result of a new mutation in the gene, which explains why neither parent was affected. Therefore the term HMSN III is no longer commonly used, having been replaced by the terms CMT 1, DSD and CHN. Occasionally DSD and CHN can be inherited in an autosomal recessive manner. There are other more complex forms of CMT in which the neuropathy is combined with other features such as deafness, visual problems, vocal cord paralysis and breathing difficulties but these are all very rare.

How does CMT affect people?

The first evidence of CMT is usually between the ages of 5 and 15 but sometimes may not be until very much later, even into middle-age. Usually the first symptom is slight difficulty in walking because of problems with picking up the feet, and this may well be noted by parents first. Many people, particularly those with CMT type I, have high arched feet (referred to as pes cavus) and this may be obvious from a very early age. It tends to become particularly noticeable at the time of the growth spurt associated with puberty. Weakness of the hands occurs in some people, but this does not usually cause symptoms until after the age of 20. Patients can experience numbness of the feet and hands (usually noticed in the feet first) which is not often troublesome, but the tendency to have cold feet is frequent. Very rarely the numbness can be severe, and it is then easy for affected individuals to injure themselves without knowing it; painless ulcers of the feet may develop as a result of poorly fitting shoes, or burns on the hand from hot cups etc. Pain is not a common feature of CMT and if present may be due to secondary effects on the joints or muscles. The reflexes (such as the knee jerk) are commonly lost. This does not cause any trouble for the individual, but is often noted early on by doctors. A few people
with CMT 1 have shakiness of the hands (tremor) and the combination of tremor and CMT is sometimes referred to as the Roussy-Levy Syndrome. Mild curvature of the spine (scoliosis) occurs in some people and tends to be more severe in those with early onset of limb problems. The types of CMT which run through the generations in families (see section on dominant inheritance) are not usually severely disabling disorders and often do not change a great deal after people have finished growing. It is unusual for people with CMT to lose the ability to walk, although some older people need a stick or other walking aids. It is important to stress that the disorder often varies enormously in severity, even in members of the same family, and 10 to 20% of affected individuals have no symptoms at all but are found to have evidence of the condition on examination or using electrical tests.

How is CMT inherited?

The commonest forms of CMT are inherited in a way that is referred to as autosomal dominant (AD). This type of inheritance is the most common type in CMT 1 and CMT 2. We all have two copies of every gene and in AD inheritance, the affected person has one abnormal gene and one normal gene. Each child will only inherit one gene from an affected parent (the other gene will come from the other parent) and therefore each child of an affected parent has a 50% chance of inheriting the abnormal gene and being affected. People of either sex can have the condition. However in occasional families with CMT 1 and CMT 2 the inheritance is autosomal recessive (AR). In AR inheritance a person needs two abnormal copies of the gene to be affected unlike AD
inheritance where the person only needs one copy of the abnormal gene to be affected (see above). AR inheritance is only seen if both parents are ‘carriers' of the faulty gene but these parents do not themselves have any symptoms. Both parents therefore have one abnormal and one normal copy of the gene. The condition develops only if a child inherits the abnormal gene in a double dose, i.e. one from each parent. Each child of such parents has a 25% chance of inheriting an abnormal copy form both parents (double dose) and being affected. Each child of such parents will have a 50% chance of inheriting one abnormal copy of the gene from either parent and be a “carrier” of the condition and each child will have a 25% chance of inheriting two normal genes (one from each parent). Males and females can be affected. Many people with autosomal recessive CMT do not have affected relatives as each child has only a 1 in 4 chance of being affected and most families are quite small. It is therefore common for only one child to be affected.
In some families, CMT is caused by an X-linked gene (X-linked inheritance) which is carried on the X chromosome, one of the so-called sex chromosomes which determine the sex of the child (females are XX, males are XY). The result is that boys inherit the disease from their mothers who are known as carriers. Carriers may show no sign of disease, although sometimes they are mildly affected, but each of their sons has a 50% chance of having CMT and each of their daughters has a 50% chance of being a carrier. Affected males cannot transmit the disease to their sons. In these families therefore, males are more severely affected than females and males cannot pass on the disease to their sons.
It is very important to establish exactly what type of CMT someone has, and to investigate family members, as advice given in genetic counselling will vary depending on the type of CMT and its mode of inheritance. This may require detailed family investigations, as some mildly affected family members may not have any symptoms.

What is the cause of CMT?

There have been major advances in the last decade in the identification of the causative genes for
CMT. To date there have been 16 causative genes identified and at least 8 other loci (location on a chromosome where a causative gene is but where the causative gene has not been identified). Most of these genes have been identified for CMT 1 and at the moment patients with CMT are more likely to have the causative gene identified if they have CMT 1 rather than CMT 2. In most families with dominantly inherited CMT I, the abnormal gene is located on chromosome number 17. This variety of CMT is called CMT IA and is due to abnormalities in a protein found in myelin called peripheral myelin protein 22 (PMP-22). The commonest genetic abnormality of the PMP-22 gene in patients with CMT 1A is unusual; affected people have an extra copy of the gene (3 copies) because they have an extra copy of a small part of chromosome 17 containing the
PMP-22 gene. Although this genetic abnormality, commonly called the chromosome 17 duplication, is usually inherited in an autosomal dominant manner, it has been found in some individuals with normal parents (and thus represents a new mutation). Rarely patients with CMT 1A have a different abnormality (a mutation) of the PMP-22 gene. About three-quarters of patients with CMT I have type IA. The second commonest form of CMT 1 is CMT 1X, where patients have a mutation of the connexin 32 gene on the X chromosome. In recent years this form of CMT has been diagnosed more commonly as doctors recognise X-linked inheritance in families.
The third well recognised type of AD CMT 1 is CMT 1B where patients have a mutation in a gene
(myelin protein zero, P0) on chromosome 1. Recently mutations in five genes have been described in autosomal dominant CMT 2. Unlike CMT 1, there is no one gene that affects most patients and it has yet to be determined how common mutations in these five genes will be as a cause of CMT 2. Interestingly, occasionally mutations in myelin protein zero (P0), which usually causes CMT 1B, can cause CMT 2. The exact reason for this is not known yet.
Mutations have now been described in seven genes causing autosomal recessive CMT 1 and CMT 2 (excluding the rare cases of DSD and CHN that can be autosomal recessive). Most of these have been described very recently and it remains to be seen how commonly mutations in these genes will cause AR CMT 1 and AR CMT 2.
It is important for patients with CMT to know which genes are currently available for testing in the UK. Testing for the chromosome 17 duplication referred to above, which causes most cases of CMT1A, is widely available in most regional genetic laboratories. Testing is also easily obtained for CMT 1X (connexin 32), PMP-22 mutations (CMT 1A) and P0 (CMT1B and CMT 2). Testing for all of the other AD CMT 2 genes and all of the AR CMT 1 and AR CMT 2 genes is not yet routinely available but for individual genes testing may be available on a research basis.
Problems and management There is no specific treatment at present for the underlying genetic defect in CMT even in those patients in whom a genetic diagnosis has been made although there are many groups researching this area. This does not mean that patients with CMT cannot be treated or helped in many other ways. It is very important that problems patients experience such as foot problems are addressed appropriately and this may greatly improve a patient’s quality of life. Accurate genetic diagnosis and genetic counselling is the other area of management in which there has been rapid development in recent years. One of the most common problems in CMT is difficulty in getting well fitting shoes because of the arched feet. It is important to wear shoes with good support, and arch supports or other devices within the shoes may be needed. In people who have quite a lot of weakness of the leg muscles, splints are often very helpful to reduce the tendency of the foot to drop. New types of splints are continually being developed and patients should discuss the options with their physiotherapist.
Ideally children and teenagers with CMT should be seen annually by a neurologist or a paediatrician to ensure that severe problems with the feet do not develop. Surgery may be helpful for very highly arched feet, either to reduce the arch and the curling of the toes which often goes with it, or to fuse together some of the foot bones. After procedures of this sort, and any other operation, it is essential to minimise periods spent in bed, as increased difficulties in walking are often noticed afterwards. Just as rest may enhance difficulty in walking, active exercise and maintaining fitness help to maintain mobility. Surgery is not usually needed for scoliosis but may have to be considered in the very few cases in which this is severe. In those with a lot of numbness of the feet, it is important to take great care of the feet, washing and drying them carefully, and inspecting the skin for small ulcers. The inside of the shoes should be shaken out to remove small stones etc., and the insides felt for irregularities that could damage the skin.
Accurate genetic counselling is one of the mainstays of management and typically involves detailed assessment, including blood and electrical tests of close relatives. Despite the major advances in understanding the genetic abnormalities in CMT, the electrical studies remain the initial and most important tool in the diagnosis of most patients. In CMT 1A, affected children will show the typical electrical abnormality from about the age of 5 years. Once a genetic diagnosis is made in a patient with CMT, the blood test can then be used to diagnose other affected members of a family. Occasionally members of a family with CMT without signs of the disease or electrical abnormalities request a genetic test to see if they are likely to develop the disease in the future (predictive testing). This is usually not done in unaffected children, the preference being to wait until they are adult and can make their own decision about testing. The interpretation of predictive testing can be difficult in rare causes of CMT as the information is not always available about whether having an abnormal gene means that a person will always develop the disease.
Predictive testing needs to be discussed on an individual basis for each patient. In some families blood tests can be used for pre-natal diagnosis by analysing a small sample of the placenta taken at about 10 weeks of pregnancy. Couples wishing to consider this option should make enquiries through their regional clinical genetics centre before embarking on a pregnancy.

Central core disease

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Central core disease falls under the umbrella of congenital myopathies which are characterised by muscle weakness and wasting. It is a rare condition, and symptoms are usually present at birth or during early infancy. These include hypotonia (floppiness), delayed motor evelopments, and muscle weakness and cramps. It is generally thought to be non- or slowly progressive, and most children affected are eventually able to walk. Some children show improvement over time, and increased muscle tone.
Central core disease is closely associated with malignant hyperthermia, a serious acute reaction
to general anaesthetics which is potentially fatal. It is triggered by muscle relaxants and inhaled
anaesthetics.

What is central core disease?

Central core disease falls under the category of congenital myopathies which are a group of conditions characterised by muscle weakness and wasting. Central core disease is a rare condition and symptoms usually become apparent at birth or early infancy, although cases have
been reported where symptoms are present in the foetus. The condition is generally non- or slowly progressive and people affected usually have a normal life span.

What causes it?

In some families, central core disease is caused by an error in the ryanodine receptor (RYR1) gene, located on chromosome 19q13. This gene produces a protein which is involved in calcium release in muscle. It is not known exactly how errors in this gene cause the condition. In many other families, the genetic cause has not been determined.
Central core disease is inherited in an autosomal dominant pattern, although many cases occur sporadically, sometimes caused by recessive inheritance with no previous family history.
Autosomal dominant inheritance means if a parent has the condition, there is a 50% chance that each child will have the condition also. Either parent can pass on the error, and both male and female children can be affected.
More information on genetic inheritance is available in our factsheet ‘Inheritance and the Muscular Dystrophies’.

What are the common features?

In most cases symptoms become apparent at birth or shortly after, and include hypotonia (floppiness) and weakness of the muscles closest to the trunk of the body. There is often a delay in achieving motor milestones, but the majority of people affected should eventually be able to walk. Muscle cramps are common and mild facial weakness has been seen in some cases, specifically involving the eyes. Weakness round the hips can lead to hip dislocations or tightening of the joints (contractures), particularly the knees and hips. Curvature of the spine (scoliosis) may also occur. Generally the heart and respiratory function are not affected.
Malignant hyperthermia (MH) is an acute reaction triggered by certain general anaesthetics or muscle relaxants (which are used for general anaesthesia). Symptoms of MH include high fever, muscle rigidity, dark brown colouration of urine and acute kidney failure. MH is potentially fatal if not treated immediately with a drug called dantrolene. MH can be prevented by avoiding the triggering anaesthetic agents with alternative drugs. Local anaesthetics are quite safe. Both MH
and central core disease are associated with abnormalities in the RYR1 gene thus it is important
to inform the consultant surgeon or anaesthetist if surgery is being considered.

How is it diagnosed?

Muscle biopsy. Generally, diagnosis is made through a muscle biopsy. A sample of muscle is taken, and examined under a microscope. This is done in one of two ways: either a small piece of muscle is taken under general anaesthetic (avoiding the drugs which precipitate MH) or a needle biopsy is performed to remove a small sample.
Muscle from people affected by central core disease has a distinctive pattern with core structures centrally located within the muscle cells. It is important to note that these structures are also seen in other, unrelated conditions. For this reason, the muscle sample must be considered along with the physical signs and/or molecular tests, in order for a diagnosis of central core disease to be made. A fact sheet on Muscle biopsies is available from the Information and Support Line.
Molecular testing. In families where the mutation is known to occur in the RYR1 gene, molecular testing is available. This involves taking a blood sample and analysing the DNA for the presence of a mutation. This process can take up to several months to complete.

What other tests are available?

Prenatal diagnosis is available for families where the mutation has been identified as being in the RYR1 gene. The technique is described in the section Molecular testing, but there are two ways to obtain samples for testing:
• Amniocentesis is traditionally performed at 15 to 17 weeks into the pregnancy. Using ultrasound to visualise, a needle is inserted through the abdominal wall, and a sample of the fluid surrounding the baby (amniotic fluid) is taken.
• Chorionic villus sampling (CVS) is carried out at 10 to 11 weeks. This involves taking a sample of tissue from the placenta. Results are available earlier using this technique than amniocentesis, but the rate of spontaneous abortion is slightly higher.

How will it progress?

Central core disease is generally thought to be non- or very slowly progressive. Sometimes progression is seen in adulthood, but some people actually show an improvement over time, with reduced weakness and increased mobility.

Is there a treatment?

Currently there is no treatment for central core disease, but management of the condition is very important.
Physiotherapy. The primary aim of an individual with a neuromuscular disorder is to increase or at least maintain function and mobility. Physiotherapy can assist in doing this, and it can also maintain breathing capacity, delay the onset of curvature of the spine (scoliosis), and help prevent the development of contractures. It is important that the physiotherapist involved is familiar with the treatment of people with neuromuscular disorders.
Exercise. There is debate over whether people with neuromuscular disorders should undertake
strenuous physical exercise. Some say that putting additional strain on already weakened muscles will cause additional harm, whilst others believe that the exercise may increase muscle
strength. Insufficient evidence exists to support either, but it is believed that moderate nonweight bearing exercise such as swimming, walking or peddling may be the best solution. This sort of aerobic exercise helps to maintain a healthy cardiovascular system and a steady weight.
It is however, important that this is discussed fully with a clinician. Corrective surgery. Scoliosis, or curvature of the spine, is common with central core disease. Spinal surgery aims to correct the posture by realigning the spinal column, and involves the insertion of rods, screws or wires. There are benefits and risks associated with this surgery, and more information is available from the Information and Support Line. As with other treatments, it is very important that the options are discussed fully with a consultant or specialist, before a decision is made. In young children a spinal brace may be used and in children who do not walk moulded seating is used.

Is there a cure?

Currently there is no cure for central core disease although much research is being conducted
into all of the neuromuscular disorders. Although there is no effective treatment, there are a
number of different ways in which to manage the symptoms of central core disease and these
are outlined above.

What research is currently being done?

Researchers world-wide are exploring many avenues in an attempt to develop more effective treatments and hopefully a cure. The research department at the Muscular Dystrophy Campaign regularly monitors research advances in congenital myopathies, and produces releases, which are sent to members when significant scientific advances occur.

Bethlem myopathy

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What is myopathy?

The term myopathy is derived from the Greek language and means muscle disorder.
What is Bethlem myopathy?
Bethlem myopathy (BM) is a little known muscle disorder, which is named after the Dutch doctor who first described the condition in 1976. Diagnosis and recognition of it has improved over the past few years following work done by a number of researchers around the world on the
identification of the protein involved. The protein is called collagen VI. A fault in any of the three
genes for collagen VI can give rise to BM.

How does the disease present?

First symptoms of BM can present at any time from birth through to adulthood and are very variable. In childhood these symptoms can be hypotonia (floppiness), muscle weakness, delayed motor milestones (for example when a baby first sits up unaided or learns to walk), talipes (clubfoot), torticollis (stiff neck) and contractures (tightness) in the ankles, hip, knees and elbows. The contractures are often quite variable and can come and go over time. Adults with BM can have tight tendons at the back of their ankles, as well as tightness of various other joints (elbows, knees, joints in the back) and especially some of the muscles in the hands.
Other symptoms such as poor stamina/poor exercise tolerance and difficulties walking upstairs or doing tasks which require lifting the arms above the head are related to the subtle muscle weakness that tends to go with Bethlem myopathy. In addition, the skin of some people with BM
can be unusual. Over the outer surfaces of the arms and legs especially it can feel rough or dry to touch and has been described as looking like “plucked chicken skin”. Other patients might find that they scar in an unusual way, either by forming keloids (raised, rather angry looking scars) or thin silvery “cigarette paper scars”.

How is Bethlem myopathy diagnosed?

The diagnosis of BM is usually suspected from the symptoms and examination, paying special attention to the features described above. Because it is a rare disorder not very many doctors have experience of these features and people with Bethlem myopathy may often have had other diagnoses suggested in the past.
It is often necessary to do a blood test and a muscle biopsy to exclude other conditions that can present in a similar fashion. The muscle biopsy is studied through a microscope to check how the muscle is put together and whether there is any evidence of it being damaged. In BM the muscle fibres, instead of being evenly sized, show some variation but no significant damage or scarring. With special stains we can also check for a special protein called laminin beta 1, which can sometimes be reduced. However this only provides additional evidence, as these findings are not entirely specific to BM. At present the diagnosis of BM is usually made by collating the information gathered from history and clinical examination with laboratory findings.
In some cases it is possible to prove the specific diagnosis by demonstrating a fault in one of the genes encoding for collagen VI. This can be done using a skin biopsy or blood sample. At present it is available on a research basis only and results take months to years to come through. However, we are hoping this will change over the coming year.

Is Bethlem inherited?

BM is inherited in what we call an autosomal dominant way. This means that there is a 50% (one in two) chance for the children of a person affected by BM to inherit the faulty gene and be affected by BM themselves. This is independent of how mildly the parent might be affected. Sometimes when people are diagnosed as having BM, neither of their parents seems to be affected. In some cases the fault in the gene may have arisen for the first time in the affected person, which is quite a common situation.

Are there any risks of developing any complications?

The main complications to look out for at the regular check ups in the muscle clinic are contractures (muscle tightness causing restrictions in the range of joint movement) and chest problems. People with BM can be prone to chest infections if their cough is not strong due to weakness of their breathing muscles and in some cases overnight sleep studies may be required to assess breathing. From what we know so far the heart, although a muscle, is usually not affected by BM. It is important to note that collagen VI mutations cause a more severe condition as well called Ullrich congenital muscular dystrophy.

Does the condition get worse?

For most patients with BM the weakness and contractures are known to get worse over the years, however, this usually only happens very slowly. Whereas some adults remain unaware of any muscle weakness and only have very slight contractures which do not pose them any functional problems others need to make use of practical home aids to work around their muscle
weakness and contractures. A proportion of adults over the years might need aids to help movements (for example, cane, crutches or wheelchair) outside the house and might also experience breathing problems for which they require treatment.

Is there a treatment or cure?

At the moment, there is no cure, nor any specific drug treatment for Bethlem myopathy. However, there are ways, described below, of helping to alleviate the effects of the condition and to prevent complications from occurring.

What help can be offered?

Physiotherapy is one of the main forms of help. A programme of exercises is usually worked out with a physiotherapist at the time of the diagnosis to stretch tight joints and help to maintain suppleness and keep muscles flexible. It is important to keep a close eye on mobility and joints and this can be done in conjunction with the local physiotherapy team as well as through regular check-ups with your consultant or muscle clinic. Occasionally surgery to release the Achilles tendon can help a person with BM to stand and walk more easily. Children and adults with BM are encouraged to remain as active as possible and ensure that they do not become overweight, so that the strain imposed on their muscles is kept to a minimum.
People with BM can have chest problems if their cough is not strong. It is helpful to keep a close eye on things by doing specific breathing tests at regular intervals. Where there may be a problem, flu and pneumovax immunisations are advisable. It also important, that every chest infection is treated promptly with antibiotics.
Constipation, possibly due to the fact that a person is not very active, can be a problem. This can be treated by high fibre diet, drinking plenty of fluids and very occasionally by laxatives. Your consultant or muscle clinic may be able to give support and information to schools and other professionals where this is needed to be sure a person with BM is getting the help he or she needs. The specialised Muscular Dystrophy Campaign Care Advisors can sometimes help to liaise between the various professionals such as physiotherapists, occupational therapists, social workers and teachers and may also be able to put you in touch with like-minded people in similar positions.

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Whilst every reasonable effort is made to ensure that the information in this document is complete, correct and up-to-date, this cannot be guaranteed and the Muscular Dystrophy Campaign shall not be liable whatsoever for any damages incurred as a result of its use. The Muscular Dystrophy Campaign does not necessarily endorse the services provided by the organisations listed in our factsheets.

Becker muscular dystrophy

2010-02-04T12:14:00.000-08:00

Becker muscular dystrophy

What is Becker muscular dystrophy?

The muscular dystrophies are a group of genetic disorders, which cause muscle weakness. The Becker type was first recognised in 1956 and is now known to be a much milder variant of the better known Duchenne type of md. Becker md is generally slowly progressive and affects only males.

What causes it?

A fault in a particular gene (dystrophin) carried on the X chromosome leads to the formation of a faulty protein in muscle fibres. This protein, also called dystrophin, is absent or severely abnormal in Duchenne md. In Becker md a milder fault makes the dystrophin molecule smaller (or occasionally larger) or less abundant than normal. When dystrophin is abnormal the muscle fibres gradually break down and the muscles slowly become weaker. These dystrophin
abnormalities in muscle provide a very good test for the diagnosis of Becker MD.

What are the symptoms?

The average age at diagnosis in BMD is 11 years but the range is very wide - sometimes the diagnosis may be made in early childhood or well into adult life. Symptoms usually begin very mildly in childhood; often cramps on exercise are the only problem at first but a few affected boys are late in learning to walk. Most people with BMD are not very athletic in childhood, and many struggle with school sport. Later, in the teens or twenties, muscle weakness becomes more evident causing difficulty in rapid walking, running and climbing stairs. Later still it may be difficult to lift heavy objects above waist level.
Men with typical Becker dystrophy may become unable to walk in their 40s or 50s or even later but there are less frequent and more rapidly progressive variants of Becker dystrophy in which this may happen in the 20s or 30s. Over a period of many years some muscles become weak and wasted, especially certain muscles of the shoulders, upper arms and thighs, while others that are less weak are often enlarged - this is usually particularly noticeable in the calf muscles.
The muscles of facial expression, speech and swallowing and the involuntary muscles (for example those of the bowel and bladder) are not affected in Becker MD It is important to be aware that some people with BMD may have problems with their heart (see the 'heart check' leaflet), and in the long term with the breathing muscles. These often do not cause any
symptoms, and watching out for these problems, which can often be treated, is an important reason to keep in touch with a specialist clinic.

Is there a cure?

Unfortunately there is no cure at present. Research is proceeding to try to find a way to induce the muscles to form dystrophin. Any treatment, which may be found to be effective in Duchenne MD, would theoretically be effective also in the Becker type.

So what can be done?

Active exercise strengthens normal muscle fibres (and the great majority are normal in the early years of Becker MD). It is important to try to keep as fit and active as possible. Regular daily exercise is better than occasional sudden bouts of exertion.
Cramps during exercise can bother people with Becker MD at some stage - often especially as a teenager. If they are very troublesome it may be worth experimenting with ‘night splints’ (plastic splints to maintain a gentle stretch of the calf muscles overnight) or with sessions of calf muscle massage or compression with air-filled boots though there is not yet a properly tried and tested treatment for cramps.
In the later stages a wheelchair is likely to be needed at least for getting about independently over long distances. There is a great deal of other equipment that may be useful to individuals and much can be done to help both at home and at work to make certain tasks easier by careful choice of furniture, bathroom equipment etc. Advice and help with these matters is increasingly available and the Muscular Dystrophy Campaign will be able to put you in touch with the best sources of advice.

What about school?

Most young men with Becker md leave school without having had any major muscle problems except that they are usually slow at running in their teens and not very successful at PE or games. However, sometimes if cramps are a particular problem, keeping the school informed can be a good idea. In many cases the problem is recognised and diagnosed at around the age of 20.
A few boys with Becker md also have learning problems, usually of a mild degree but sufficient sometimes to limit their academic success at school. It is important to realise that this is not true of most affected boys, but when the problem does exist it is sensible to recognise and assess it early and to arrange the best possible plan to provide the right educational help. Unlike the muscle weakness, any learning problem will not get worse as the years go by. Despite the fact that to the outside observer BMD may cause relatively few problems in childhood, there is no doubt that some boys can find it a major psychological problem to be poor at sport in a society where boys are especially encouraged to pursue excellence at sport and where sporting heroes are so much in the news. Promoting self worth in this period is a crucial factor.

What about work?

People with Becker md have been employed in a range of jobs from steel workers to research scientist though occupations requiring a considerable amount of physical activity are not feasible for most people who have Becker md. It is clearly important for people to plan their careers on the basis that their existing physical capabilities are unlikely to improve and will eventually gradually decline. There is no reason why people with BMD should not work - if any special provisions are necessary the local clinic or family care officer can put you in touch with the right people at the local careers service.
The important principles are to work for the best possible educational qualifications at school, to make good use of any opportunities for further education and then either to plan a career that will depend as little as possible on physical strength and mobility, or to be prepared to re-train and change jobs appropriately as time goes on.

How is Becker md inherited?

The disorder is inherited as an X-linked recessive trait, which means that it affects only males
but may be transmitted by unaffected female carriers of the gene to their sons. The sons of carriers each have a 50:50 chance of being affected. The daughters of carriers each have a 50:50 chance of being carriers. The mothers and sisters of affected males may be carriers and may need to be tested. The sons of affected males do not carry the gene and will not be affected or transmit the gene. However, all the daughters of affected males are carriers of the gene and may transmit the disorder to the following generation.

How early can it be diagnosed?

Once Becker dystrophy is known to affect one male in a family it is possible by simple blood tests to identify it or rule it out in any other boys at risk from birth onwards. In most families, but not in all, prenatal diagnosis is also possible, but this is more difficult and if at all possible the situation needs to be fully assessed before a pregnancy is embarked upon.

Can any carriers in the family be identified?

Most carriers can be detected if blood samples from their affected male relatives and certain other key members of the family are available for comparison, using techniques of DNA analysis. Although a simpler blood test for creatine kinase is positive in many carriers, only the DNA studies can rule out the carrier state in a woman at risk (for example in the sister of an affected man). However, in a few families, or if the key samples from relatives are not available, it may be possible only to calculate for each potential carrier her statistical risk of having an affected son.