Types of Muscular Dystrophy
Duchenne Muscular Dystrophy
1. Is Duchenne Muscular Dystrophy also known by other names?
No, it is only known as Duchenne Muscular Dystrophy or by its abbreviation DMD.
2. What is Duchenne Muscular Dystrophy?
It is one of the most frequent forms of muscular dystrophy, affecting approximately 1 in 3500 male births. It was described in 1861 by a French Neurologist, Guilluame Benjamin Amand Duchenne and was named after him. He was one of the first people to study the muscular dystrophies. DMD is an X-linked inherited disorder and affected individuals are generally boys, with girls being carriers of the faulty gene. A milder variant of this disorder is known as Becker MD (Please note that a separate MDF Fact Sheet is available on Becker MD).
3. What causes Duchenne Muscular Dystrophy?
DMD is caused by a fault in the dystrophin gene, located on the X-chromosome. This leads to the formation of a faulty protein in muscle fibres. This protein, called dystrophin, is absent or severely abnormal in Duchenne muscular dystrophy (DMD). In Becker muscular dystrophy a milder fault makes the dystrophin molecule smaller (occasionally larger) or less abundant than normal. The function of dystrophin in the muscle fibre is not yet understood, but when it is abnormal the muscle fibres gradually break down and the muscles slowly become weaker
Typically boys inherit this gene (with the X chromosome) from their mothers, who are generally not affected. For this reason only boys are affected (with extremely rare exceptions). When the faulty gene is passed on to a girl from her mother (referred to as a carrier) she will also be a carrier of this faulty gene and can, therefore, have affected sons. It is estimated that 20-30% of affected individuals are the first of their generation, they are referred to as “new gene mutations”.4. What are the symptoms and which muscles are affected?
Most affected boys develop the first sign, which is difficulty in walking, at the age of 1 to 3 years. Some of these boys may also have had language delay (the protein dystrophin is also expressed in the brain). Without intervention, by approximately 8 to 11 years (rarely earlier or sometimes a little later) they become unable to walk, and by their late teens to early twenties the weakness is usually serious enough to put their lives at risk. The first thing parents usually notice is that the calf muscles are enlarged. Sometimes the diagnosis of Duchenne Muscular Dystrophy is not made until school-going age. By then difficulty in walking is usually obvious. DMD boys often walk on their toes with their abdomen pushed forwards and with a waddling gait. These are early hallmarks of the disorder and result from weakness of muscles of the pelvis, which normally extend the hips in order to retain the upright position when standing. When these muscles are weak there is a tendency for the pelvis to tilt forward and in order to compensate for this the affected boys lean back and the abdomen protrudes forward (called lordosis). Rising from the floor unaided also becomes increasingly difficult which is also due to weakness of the muscles around the hips and thighs. This results in what is referred to as Gower's sign (difficulty in rising from the floor resulting in the boy climbing up his legs with his hands to become upright), after the physician who first described it.
At the same time as weakness of the hip muscles becomes evident, there is also weakness of the shoulder muscles so that the affected boy has increasing difficulty raising his arms. Affected boys usually become confined to a wheelchair by the age of 12-14 years, as weakness of the hips and thighs progresses. Thereafter, the rate of progression of the disorder usually becomes less obvious. Most muscle groups later become affected. The eye, chewing and swallowing muscles are, however, unaffected. The confinement to a wheelchair increases the likelihood of contractures developing as a result of immobility. The sole of the foot often turns inward, which is referred to as talipes. Later the legs and arms can no longer be straightened out due to flexion contractures of the knees and elbows. The prolonged sitting in one position results in the gradual curvature of the spine to one side (scoliosis) and so compresses the lung on that side. This is referred to as scoliosis and can result in serious problems with breathing and chest infection. Respiratory problems are in fact the main cause of death, although these are the result of a combination of pathologies – namely overall weakness, scoliosis and cardiomyopathy. The heart is also affected in DMD and this may aggravate any respiratory problems. In general, up to a third of boys with Duchenne Muscular Dystrophy have some degree of intellectual impairment (from very mild to more severe). This is particularly reflected in poor reading ability, word comprehension, and memory skills. This intellectual impairment is not related to muscle weakness and is not progressive.5. How is Duchenne Muscular Dystrophy inherited?
Duchenne Muscular Dystrophy is inherited as a so-called X-linked recessive trait. This means that it affects boys predominantly but may be transmitted by unaffected female carriers of the gene to their sons, and thus mothers of affected boys are often carriers. This difference exists because girls have two X-chromosomes and boys have one X and one Y-chromosome. 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.
There are, however, many families with no obvious family history. In these, a so-called new mutation has arisen, but other relatives may still be at risk.
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 counselling and appropriate tests for those members of the family who are at risk of being carriers. A very small number of female carriers of the gene have a mild degree of muscle weakness themselves and are then known as 'manifesting carriers'. However, it is extremely rare for a female to show symptoms. The signs may even present as a pattern of "limb girdle" weakness.
As this is a genetic condition, genetic counselling is strongly recommended. Genetic counselling provides information on the inheritance pattern, risks to other family members, prognosis, psycho-social support, as well as information about diagnostic testing, carrier testing, preclinical and prenatal testing (where available).6. How is Duchenne Muscular Dystrophy diagnosed?
Reliable tests are available once the diagnosis of DMD has been suggested in a boy. Affected boys have very abnormally high levels of an enzyme called creatine kinase (CK) in their blood. Most hospital laboratories can perform the CK test. However, the CK test is not specific to DMD and many other causes for a raised creatine kinase test exist.
For a specific diagnosis of DMD, in families with no previous affected member, DNA testing and if negative a muscle biopsy is generally regarded as essential. DNA testing can be undertaken in specialised genetic units on a blood test. (Centres in SA: Molecular genetics department UCT, Cape Town; Department of Human Genetics, University of the Witwatersrand, Johannesburg) In about two thirds of boys with Duchenne Muscular Dystrophy a deletion (or missing piece) from the Duchenne gene can be identified by this test. If a clear deletion is identified, no further confirmatory testing is necessary. Thus DNA testing should be carried out prior to muscle biopsy as it is non-invasive and may obviate the need for an invasive biopsy if the diagnosis is confirmed.
Only specialised hospital departments have the facilities for doing muscle biopsies of a high enough quality to give fully reliable results. Nowadays measurement of dystrophin in muscle is being increasingly used in specialised units but it is not usually essential for the diagnosis.
Once DMD is known to affect one male in a family it is possible to identify it or rule it out in any other boys at risk. 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.
One of the most important things that need to be done soon after the diagnosis of a boy with Duchenne Muscular Dystrophy is to seek genetic counselling and appropriate tests for those members of the family who are at risk of being carriers. However there are ethical implications where juvenile females should not automatically undergo testing without full understanding and consent being gained – this is usually only appropriate when they reach their majority and are of child-bearing age.
7. Can carriers 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 some carriers, only the DNA studies can rule out the carrier state in a woman at risk (for example in the sister of an affected boy). However in a few families, or if the key blood samples from relatives are not available, it may only be possible to calculate for each potential carrier her statistical risk of having an affected son.
Genetic counselling forms an important part of the support that the affected individual, carriers and the families need.8. What is a manifesting female carrier?
Women who can transmit the gene for Duchenne or Becker muscular dystrophy are known as carriers. Usually they have no muscle weakness, but occasionally they have a relatively mild form of muscular dystrophy and are then known as manifesting carriers. Known carrier females are advised to have a routine cardiac review to assess their cardiac function. If they have no near male relative who happens to be affected, the true nature of their weakness may be far from obvious and very difficult to identify and they may have been diagnosed as having "Limb Girdle Muscular Dystrophy" or another type of muscular dystrophy. The measurement of dystrophin on muscle biopsies is very useful for diagnosis in such instances. However these women have a 50% chance each time they have a son that he will have Duchenne MD, so the diagnosis is important. Women diagnosed as having Limb Girdle Muscular Dystrophy, especially if they have no family history of MD, should seek specialist advice about this possibility. Research in molecular biology and on dystrophin in the next few years may help to make diagnosis easier - at present it requires rather specialised and laborious laboratory techniques. A very rare and special category of manifesting carriers has identifiable chromosome anomalies which are helpful in diagnosis.
9. Can we be sure there is no mistake in the diagnosis?
Assuming the diagnosis of DMD has been made by an experienced clinician, there are only three conditions which are at all likely to cause any confusion in diagnosis to a doctor experienced in DMD diagnoses - and both these are other types of muscular dystrophy (Limb girdle muscular dystrophy, Becker Muscular dystrophy and Emery Dryfuss Muscular dystrophy). The autosomal recessive type is about 40 times more rare than the Duchenne type in boys and is somewhat similar, but dystrophin levels in the muscle are normal. The Becker type of muscular dystrophy is a milder variant of dystrophin deficiency and there is an overlap in severity with the Duchenne type. DMD is about three times more frequent that Becker. It may be difficult in very young children to gauge the severity at first but in the great majority of cases the diagnosis is clear. In the mildest forms of Duchenne and the most severe forms of Becker the distinction lies only in the name
10. Is there a cure or treatment?
Unfortunately no cure has yet been discovered. Much can be done to help limit the effects of the muscular dystrophy but no treatment is known which affects the actual loss of muscle cells. Steroids may help to delay disease progression, but should only be used under strict supervision of a clinician experienced in their use in DMD. One of the main challenges in the treatment of affected individuals who become confined to a wheelchair is to prevent scoliosis. This can be achieved to some extent by always adopting an upright sitting position and the use of a back support - but perhaps more effectively by surgery in some instances. Intensive research to find a cure has been done for many years. The discovery of dystrophin in 1987 has given a new impetus because scientists now have a practical starting point in their search for a cure. No one can predict how soon this may be achieved or which of the new ideas that are constantly being tested will prove worthwhile. Current research is ongoing into a product PTC 124 that will allow “read through” of mutations and potential start dystrophin production again. These is only likely to be effective for a relatively small number of affected patients with very specific mutations (estimated 6%), but the methodology should allow other mutations to be addressed by similar methods of intervention. Local centres have been instructed to ensure all genetic results on children are comprehensive so that if the product is effective early access to suitable children will be possible.
The following approach is policy at the Neuromuscular service at Red Cross Children’s Hospital. Parents / carers and children are educated from presentation to avoid tightening of their tendo-achilles and hamstrings by a home program of daily stretches. As soon as the children have evidence of motor disability, following international guidelines, prophylactic steroids are introduced. Children are monitored on a three monthly basis to ensure side effects from the steroids are avoided and to monitor their muscle power. There is evidence that the steroids prolong ambulation by 2-3 years. This additional time results in many of the children already having undergone a growth spurt prior to loss of walking. Becoming wheelchair bound at this stage, provided the seating support is adequate avoids severe scoliosis developing. Throughout their care the children undergo regular cardiac assessments (2 yearly when ambulant and yearly once wheelchair bound unless concern arises beforehand). Prophylactic intervention with low dose ACE inhibitors is introduced and more aggressive treatment started if any evidence of cardiac compromise identified. During the years attending the clinic families are encouraged to take control of various life areas, primarily as regards education, home facilities and the future (when the child becomes more dependent). An ideal school facility would have access to ancillary services such as physiotherapy, occupational therapy, speech therapy and dietician. The facility should be wheelchair friendly and the child should be ideally in an electric wheelchair so his energies are directed at school work rather than pushing himself between lessons. Avoidance of excessive weight gain is essential and often a problem when the child losses ambulation. As the condition progresses the child, generally into his late teens, is at risk of developing nocturnal hypoventilation. This is a traumatic stage in the condition and the boy may be noted to loose weight rapidly, wake frequently during the night breathless and have daytime drowsiness and headaches. Fairly simply testing screens can confirm this if it is suspected and nocturnal BIPAP can significantly improve the boy’s quality of life.11. What can we as parents do to help him?
Learn all you can about muscular dystrophy and be prepared to go on learning over the years. It will give you confidence and help you to foresee and prevent problems and to make balanced decisions. Help him to enjoy active exercise so that it becomes a life-long habit; don't worry about how much it is helping the muscles at first. Active exercise means making the muscles work quite hard (but without overdoing it) and this helps to strengthen them. Games, swimming and walking for pleasure are some of the best ways to start. Passive exercise means stretching and it becomes necessary a bit later (usually with the help and advice of a physiotherapist) to prevent contractures. Think about the whole family's eating habits. A healthy diet will prevent excess weight gain and prevention is far easier than cure. As boys with Duchenne muscular dystrophy become less active they often gain weight because they need much less food than their active friends and siblings, and yet they often go on eating as much as ever. Tobacco smoke can be quite harmful to a child's lungs especially if he already has difficulty breathing. Avoiding exposure to smoke will help towards minimising problems with his chest during his late years. Make sure that his life is packed full of interesting activities, hobbies and friendships, keep open house to all his friends, encourage his education, his skills and his independence and make sure that your other children share in these benefits.
12. Is there a risk during anaesthesia?
Yes, individuals affected with DMD have muscle weakness and this can cause problems during anaesthesia. In addition, they are at risk of developing Malignant Hyperthermia during anaesthesia. It is always recommended that the presence of a muscular disorder be mentioned to your doctor.
13. Has research been conducted on DMD in South Africa?
Yes, an extensive research programme is conducted on DMD (and Becker MD) at the department of Human Genetics at the University of Cape Town and the Department of Neurology at the University of Natal, Durban. This programme aims to discover the genetic basis of DMD in the South African population, and also offers a DNA diagnostic service.
14. The role of the Muscular Dystrophy Foundation (MDF) in South Africa
The MDF supports individuals affected by muscular dystrophy and their families by offering emotional support, information - including a series of fact sheets, referrals to genetic counseling and other clinics, formation of support groups, assistance with special equipment, when possible, as well as financial support for research projects in muscular dystrophy in South Africa. Creating public awareness for muscular dystrophy is also an important aspect of our work, since the MDF relies solely on contributions from its members and other donors to provide an on-going support service. Through our newsletter members are kept informed of all the activities and receive national and international research updates. Please contact any office of the MDF if you require information about any of our activities or programs.
15. Where can we find assistance?
Please contact your local MDF office for further information:
MDF Website: Please visit our MDF website (www.mdsa.org.za) for muscular dystrophy news updates.
16. Please note
The treatments and drugs mentioned in this fact sheet are for information purposes ONLY. Please consult your physician or other health care specialist for information regarding the use of any of the above. The MDF encourages duplication of this fact sheet, under the following condition: that it is duplicated in its entirety - including the MDF logo and full text. Only individuals authorised by the MDF may make changes to this fact sheet (the information "updated by" and "last update" should be completed). Alterations to this fact sheet by any other party are strictly prohibited.
This fact sheet was adapted from the following source(s): Fact sheet(s) of the Muscular Dystrophy Group of Great Britain and Northern Ireland.
Compiled by: MDF-Gauteng Branch
Updated by: Dr J Wilmshurst - Neuromuscular service – Red Cross Children’s Hospital
Approved and Released by: National Office of the MDF
Last update: June 2008
