Duchenne Muscular Dystrophy
Fact Sheet # 04
Is Duchenne Muscular Dystrophy also known by other names?
No, it is only known as Duchenne Muscular Dystrophy or by its abbreviation DMD.
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).
What causes Duchenne Muscular Dystrophy?
DMD is caused by a fault in a gene that is located on the X-chromosome. 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). DMD is known to result from a defect in a single important protein in muscle fibres called dystrophin. When the faulty gene is passed on to a girl from her mother (referred to as carriers) she will also be a carrier of this faulty gene and can, therefore, have affected sons.
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. 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 perhaps 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 to 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 boy pushes his abdomen forward (called lordosis) and his shoulders backward. Rising from the floor unaided also becomes increasingly difficult which is also due to weakness of the muscles around the hips. This results in what is referred to as Gower’s sign (difficulty in rising from the floor), 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, 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 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. 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.
How is Duchenne Muscular Dystrophy inherited?
Duchenne Muscular Dystrophy is caused by an X-linked gene (that is, the gene is on the X‑chromosome; girls have two X-chromosome and boys have one X and one Y-chromosome). This means that predominantly or mostly only boys are affected but that their mothers are often 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 - this is referred to as a 'spontaneous mutation'. These types of mutations are difficult, and sometimes impossible, to prove and can be decided only after careful and expert assessment of the family. In about two thirds of all cases the mother carries the gene but is not affected by it. Such women are known as ‘carriers’. Each subsequent son of a carrier has a 50% chance of being affected and each daughter has a 50% chance of being a carrier herself. 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. A 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).
How is Duchenne Muscular Dystrophy diagnosed?
Reliable tests are available once a boy has been diagnosed as being affected by DMD. 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, a muscle biopsy (or DNA testing) is generally regarded as essential. 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. In addition a quite separate blood test can be done in specialised genetic units to examine DNA. 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. In the future, and as we become more familiar with the significance of their particular deletion in predicting the likely severity of the muscular dystrophy in each individual, we may be able to make confident diagnoses without a muscle biopsy being necessary. However, this will only be possible for those boys who have a clear-cut deletion.
Can carriers be identified?: It is less easy but geneticists can identify from the family tree which women are at risk of being carriers. A combination of CK and DNA blood tests will allow the great majority of female carriers to be either identified as carriers or given a strong reassurance that their risk is very low. The carriers are thus also identified via the DNA test, and genetic counselling forms an important part of the support that the affected individual, carriers and the families need.
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. 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". 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 (translocations) which are helpful in diagnosis.
Can we be sure there is no mistake in the diagnosis?: There are only two 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. The autosomal recessive type is about 40 times rarer 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.
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. 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.
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.
Is there a risk during anaesthesia?
Yes, individuals affected with DMD 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.
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 UCT. This programme aims to discover the genetic basis of DMD in the South African population, and also offers a DNA diagnostic service.
Please contact your local MDF office for further information.
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