Muscular dystrophies: Duchenne and Becker
What are muscular dystrophies?
The muscular dystrophies are a group of muscle diseases which have 3 features in common: they are hereditary; they are progressive; and each causes a characteristic, selective pattern of weakness.
Why are Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) discussed together?
DMD and BMD cause similar patterns of weakness and disability and are inherited in the same way. Weakness and disability are more severe in DMD than in BMD. Becker dystrophy is like a less severe form of Duchenne dystrophy. Recently it was shown that DMD and BMD are due to defects of the same gene. The normal function of the gene is to enable muscle fibres to make a particular chemical substance, a protein called dystrophin. Muscle fibres in people affected with DMD are extremely deficient in dystrophin, in BMD the deficiency is less severe.
Duchenne muscular dystrophy (DMD)
What would make a doctor suspect DMD?
DMD affects only males, with rare exceptions. Unless a boy with DMD is known to be at risk because of his family history, he is unlikely to be diagnosed before the age of 2 or 3 years. Most boys with DMD walk alone at a later age than average. Then the parents are likely to be worried about something unusual in the way he walks, about frequent falling or about difficulty rising from the ground or difficulty going up steps. Less often, concern arises because of intellectual handicap ('mental retardation'). Although intellectual handicap affects only a minority of boys with DMD, it is more frequent than in other children.
How would the diagnosis of DMD be made?
Usually, by the time a doctor is consulted there is an effect on posture and gait, that is in the way the affected boy stands, walks, runs, especially up hills or steps. The doctor is likely to observe that the calf muscles and sometimes other muscles look very well developed or excessively large. Other muscles will be poorly developed.
There is usually a typical style of walking which can be recognised and which is something described as waddling. Whether standing still or walking, the affected boy usually has an exaggeration of the forward curve of the lower part of the back. The medical term for this is lordosis; non-medical people sometimes call it sway-back. A later development is a tendency to stand and walk on the forward part of the foot with the heels off the ground. Testing individual muscles or muscle groups reveals a pattern of weakness which is typical of DMD.
Can DMD be diagnosed before these features are obvious?
If parents have brought their son to a doctor at a very early stage of the disease, it may be difficult or impossible to detect anything definitely wrong on observing him. Doctors are therefore encouraged to test for DMD, with a blood test, whether they strongly suspect the diagnosis or regard it as just a possibility.
How does a blood test help?
The test is a measurement of the amount of a chemical, called creatine kinase, in the blood. It is a serum creatine kinase (SCK) measurement. Creatine kinase is an important chemical in muscle fibres and there is normally a small amount of it in the blood serum. (Serum is yellow fluid which is left when the blood cells have been allowed to clot and have been removed.) In DMD and BMD, creatine kinase leaks out of the muscle fibres and is therefore found in greatly increased amounts in the serum. In young boys with DMD, the SCK level is nearly always at least 5 times as high as the maximum for unaffected people. It is sometimes 50 to 100 times as high.
What is the value of the test?
- When there is reason to suspect DMD, a very high SCK level makes the diagnosis probable.
- A SCK level which is normal or only slightly raised means that the boy does not have DMD. The doctor may have to consider other muscle problems, but not DMD.
Are any other tests necessary?
The diagnosis should be confirmed by muscle biopsy. Some doctors also recommended electromyography (EMG) which is an examination of the electrical activity generated by muscle when it contracts, recorded through a needle inserted in the muscle. Muscle biopsy involves the removal of a small piece of muscle for examination. Since the discovery of the defect of dystrophin in DMD it has also been possible to arrange for muscle biopsy specimens to be examined for this specific defect.
How does Duchenne dystrophy affect people as they get older?
At the time of writing there is no cure for DMD. The worsening of disability can be slowed by such measures as physiotherapy, but it cannot be stopped. On average, use of a wheelchair proceeds from occasional use at about age 9 years to almost total dependence by the early teens, but there is a range of severity to either side of this.
As the ability to walk is lost, the function of the hands and arms becomes increasingly important in determining the affected person's abilities. Most affected people survive into their 20s. A small minority survive only to their late teens, another small number to more than 30 years of age.
Do affected people have other health problems?
Some people with DMD have additional problems. These include impaired intellectual development and problems with the joints, the spine, the heart and the function of the lungs. Intellectual handicap is more frequent in boys with DMD than in the general population but only affects a minority. Unlike the muscle weakness, it is not progressive. Whatever intelligence an affected boy has at birth, he retains it unless it is affected by something else. This is so whether he is born with superior, average or less than average intelligence.
Joints tend to become restricted in their range of movements. This is called contracture. The ankles are usually affected early, then the hips and knees and lastly the joints of the upper limbs. Physiotherapy and occupational therapy are directed against this complication. The physiotherapist advises on exercises to stretch the joints and the occupational therapist on good and bad sitting positions and activities. Surgery is sometimes used to correct contractures. Medical opinions vary as to when surgery is advisable.
Curvature of the spine is a serious complication. It is called scoliosis. It is a curvature to the side, convex to one side and concave to the other. This is accompanied by rotation of the spine and, because the ribs are attached to the rotated spine, the chest wall becomes more prominent on one side.
Scoliosis, if severe, can be uncomfortable or painful and limits the function of the lungs and the upper limbs. It is also disfiguring. Scoliosis worsens most rapidly when growth is most rapid, in the latter stages of puberty. If scoliosis is not severe by the time the peak rate of growth in height has been passed, it is unlikely to become severe.
Increasingly, scoliosis in people with DMD is treated surgically. This involves a major operation and the insertion of a metal rod to hold the spine straight. The timing of surgical treatment is critical because the ability of a person with DMD to undergo such major surgery with safety is constantly diminishing with age. A decision about surgery is often taken before the scoliosis has become severe, in anticipation that it will do so if untreated. Any suspicion that scoliosis is developing should be reported to the attending doctor or therapist.
The heart is a muscle and is affected in DMD, but usually without actually causing trouble. When the dystrophic process in the heart does cause symptoms, these usually respond to treatment.
The function of the lungs in people with DMD depends mostly on the strength of the muscles which move the chest in breathing and coughing. This usually determines the length of life for affected people, provided that the other complications do not occur.
When the muscles involved in breathing become very weak, lung function becomes inadequate so that there is not enough oxygen and too much carbon dioxide in the blood. This causes drowsiness, headaches and a general lack of well-being. When this happens, assistance with breathing through a face mask, used during sleep, may return the blood oxygen and carbon dioxide levels to normal and relieve the symptoms.
A small number of affected people choose to have mechanically assisted breathing for 24 hours a day when their breathing muscles are so weak that they could not otherwise support life.
Becker muscular dystrophy (BMD)
How is BMD different from DMD?
BMD is less severely disabling then DMD. An arbitary means of distinguishing the 2 disorders depends on whether the affected person can still walk at age 16 years. Muscle biopsy tends to show more or less severe changes, related to the severity of disability.
Since the discovery that dystrophin is defective in DMD and BMD, but more severely defective in DMD, examination of dystrophin in muscle biopsy samples can be used to distinguish them.
Are other muscular dystrophies difficult to distinguish from BMD?
Limb-girdle muscular dystrophy (LGMD), which is most often of autosomal recessive inheritance, may be difficult or impossible to distinguish from BMD which is X-linked recessive. The mode of inheritance and therefore the diagnosis may be revealed by the family tree or by blood tests (SCK) revealing carrier status in female relatives in the case of BMD. However the conclusive test to distinguish BMD and LGMD is the examination of dystrophin on the muscle biopsy specimen.
Is BMD as predictable in its progress as DMD?
DMD is fairly predictable. There is a range of severity, and disability progresses more rapidly in some people than in others. Nevertheless the range of severity is rather narrow. BMD is much more variable. Some affected people are able to walk only until early adulthood, others to an advanced age. Survival in some is to middle age but others have survived more than 80 years. Some develop heart trouble in early adulthood, others never do.
Is the severity the same within families?
There are sometimes big differences in severity of BMD, between affected individuals in the same family.
How is BMD diagnosed?
The process is like that described for DMD but the doctor's findings are in all respects generally less severe. The SCK level is increased, the EMG and muscle biopsy show changes consistent with the diagnosis. If a test for dystrophin in the muscle biopsy specimen can be arranged, the result will be diagnostic.
Are the effects of BMD on the intelligence, joints, spine, heart and lungs like those of DMD?
The intellect is not adversely affected in BMD. Like the muscle weakness, the effects of BMD on the joints and on the function of the lungs is mild in BMD compared with DMD. Scoliosis is seldom a problem because young people with BMD are usually still in relatively good condition at the time of the growth spurt at puberty. Heart trouble is less frequent in BMD than in DMD but is occasionally serious in people who are otherwise very mildly affected.
Genetic counselling in DMD and BMD
DMD and BMD are due to defects in the same gene, which is now known to be the dystrophin gene, on the X chromosome. They are inherited as X-linked recessive diseases. This means:
- only males are affected, with rare exceptions;
- female relatives of affected males may be carriers;
- the mothers of affected males, in families with more than one affected male, are carriers;
- the mothers of affected males with no affected relatives are not always carriers, because their sons may have been affected by new mutations;
- the son of a carrier has a 50 per cent probability of being affected;
- the daughter of a carrier has a 50 per cent probability of being a carrier;
- the sons of an affected male are all affected; his daughters are all carriers.
Will tests show whether an affected person's female relative is a carrier?
Sometimes tests will give a definite answer. Sometimes the best that can be achieved is a statement about the probability of carrier status.
How useful are probabilities of carrier status for a prospective mother?
Certainty is better, but probabilities are still very useful. Often the probability that a woman is a carrier is so low that the risk of muscular dystrophy to her baby is much lower than the average risk of serious birth defect or genetic disease.
How can it be certain that a woman is a carrier?
If a woman has an affected son and another affected relative, it is certain that she is a carrier. If she has 2 affected sons and no other affected relatives, it is very close to certain that she is a carrier. If a woman is a possible carrier, e.g. the sister or aunt or cousin of an affected male, a consistently abnormal SCK test, repeatedly on blood collected under proper conditions, makes it almost certain that she is a carrier.
Finally, DNA tests sometimes demonstrate carrier status with certainty or high probability.
What is DNA testing?
DNA is an abbreviation for the chemical which the genes are made of, deoxyribonucleic acid. It can be obtained from a blood specimen. DNA from a person with DMD or BMD can be tested to see if the genetic defect can be detected. If so, testing for that defect can be offered to other family members. This is called direct DNA testing.
Is the DNA defect always the same in DMD or in BMD?
The defect is always in the dystrophin gene but there are many ways in which the gene may be defective. The defect can be found by DNA testing on some but not all people with DMD or BMD.
Is DNA testing useful in a family in which the gene defect can not be found?
In such families the laboratory may be able to trace the defective gene and the normal gene through the generations by following markers called DNA polymorphisms. These are normal variants of DNA structure, close to the DMD/BMD region of the X chromosome.
If, in a family, one variant is found to be transmitted from mother to child with the normal gene, and another variant with the defective gene, the polymorphism is called 'informative', i.e. diagnostically useful. This is called indirect DNA testing.
Are direct and indirect DNA diagnostic tests equally good?
Direct testing is preferred so it is attempted first, if possible. The disadvantages of indirect testing are that:
- diagnosis is less than 100 per cent reliable;
- it is usually more time-consuming for the laboratory staff;
- any one marker is informative in only some families.
What is DNA testing used for?
It is used to determine probabilities of carrier status and also for prenatal diagnosis.
Has DNA testing replaced other tests like SCK measurement?
No. It is nearly best to combine information from all available tests.
Dr LK Shield, Department of Neurology, Royal Children's Hospital, Melbourne.
Last Reviewed: 13 June 2007
