What are Muscular Dystrophies?
The Muscular Dystrophies are a group of muscle diseases which have three features in common: they are hereditary; they are progressive; and each causes a characteristic selective pattern of weakness.
This Fact Sheet deals only with the Duchenne (type) Muscular Dystrophy (DMD) and Becker (type) Muscular Dystrophy (BMD). Please contact the Muscular Dystrophy Association for information about other types of Muscular Dystrophy and related neuromuscular disorders.
Why are DMD and 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 BMD. BMD is like a less severe form of DMD.
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, while 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 usually at a later age than average. Later on, parents and doctors should be concerned if a boy is not walking by 18 months of age and a blood test (creatine kinase) should be performed to exclude DMD. This will allow earlier diagnosis. Less often, concern arises because of intellectual disability. Although intellectual disability affects only a proportion 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 and runs, especially up hills or climbing 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 sometimes described as a waddling gait.
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 ball 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, with the central body muscles being more affected than the outer body muscles.
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 examining him. Doctors are therefore encouraged to test for DMD, which means a blood test for a start, 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 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 usually 50 or 100 times higher than the maximum - for unaffected people.
The value of the test is this:
- When there is reason to suspect DMD, a very high SCK level makes the diagnosis probable.
- An 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 is usually confirmed by muscle biopsy. This involves the removal of a small piece of muscle for examination through either a wide bore needle or a surgical incision.
The biopsy shows characteristic appearances which have been well known for many years. Since the discovery that lack of dystrophin is the basic defect in DMD, the firmest proof of diagnosis is achieved by examining the amount of dystrophin in the muscle biopsy.
In a little over half of affected people the actual defect in the dystrophin gene can be demonstrated. This is called DNA testing and is described in the section ‘What is DNA Testing?’. If a boy has typical findings of DMD and a defect is found in his dystrophin gene, the diagnosis is established. Most but not all doctors still advise that the diagnosis be further supported by a muscle biopsy to demonstrate lack of dystrophin as the ultimate proof of diagnosis.
How does DMD affect people as they get older?
At the present time there is no cure for DMD. The increasing disability can be alleviated by such measures as physiotherapy, but it cannot be stopped. On average, use of a wheelchair increases from occasional use at about age 9 years to almost total dependence by the early teens; there is, however, a range of severity on either side of this.
Recently the use of cortisone derivatives has been shown to slow the progress of DMD but at the expense of side effects.
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 twenties. 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 joints, the spine, the heart and the lungs.
Intellectual handicap is more frequent in boys with DMD than in the general population but only affects a proportion of boys. Unlike the muscle weakness, it is not progressive. Whatever intelligence an affected boy has at birth, he retains it. 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 joint 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 joint 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 metal rods (called Luque rods) 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 because of diminishing lung function. 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 may 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 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 or nose mask, used only 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. This may need to be through a tracheostomy, when a tube is inserted through the neck into the trachea.
BECKER MUSCULAR DYSTROPHY
(BMD)
How is BMD different from DMD?
BMD is less severely disabling than DMD. An arbitrary means of distinguishing the two disorders depends on whether the affected person can still walk at age 16 years. Muscle biopsy tends to show more or less severve 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 also increased, the EMG and muscle biopsy show changes consistent with the diagnosis of a dystrophy.
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 always 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% probability of being affected.
- The daughter of a carrier has a 50% probability of being a carrier.
- The sons of an affected male are all unaffected; 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 two affected sons and no other affected relatives, it is highly probable that she is a carrier.
If a woman is a possible carrier, eg 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. A normal test, however, does not exclude her being 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. This often takes the form of a ‘deletion’, a missing bit of DNA in the gene. 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 generations by following markers called DNA polymorphisms. These are normal variants of DNA structure, within or very close to the dystrophin gene.
If in a female two variants of a polymorphisim are found, it follows that each is in one of her two dystrophin genes. The variants can then be used as markers to identify her two dystrophin genes and to track them through generations of her family.
If the mother of an affected boy is known to be a carrier and if her two dystrophin genes can be identified in this way, it can be determined whether the affected boy’s sister received from their mother the same dystrophin gene as her brother. This indicates whether she has a high or a low probability of being a carrier.
When a polymorphism is present in two variants in a female it is called ‘informative’. If there is only one variant, ie the same variant in each dystrophin gene, that polymorphism does not identify the two dystrophin genes and it is called ‘non-informative’.
Using polymorphisms to track the gene defect through generations is called Indirect DNA testing. Because of the way genes and chromosomes behave when eggs and sperm are made, the interpretation of indirect DNA testing is more complex than is described above. When indirect testing is to be used, this complexity should be explained to family members by a medical geneticist.
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:
- Diagnosis is less than 100% 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 always best to combine information from all available tests.
What is the present state of research in DMD?
So far research has proceeded along two paths. The first is ‘myoblast transfer’, where early muscle cells from a close relative are grown in culture and then injected in a boy with DMD. The results so far have been disappointing in that the dystrophin has not spread to many of the muscle fibres.
The second approach has been with the animal model for Muscular Dystrophy (the MDX mouse) and has consisted of using a virus to introduce a ‘mini gene’ into the defective muscle. This work is promising, but still very preliminary.
The Muscular Dystrophy Association’s purpose and programme.
The Muscular Dystrophy Association (MDA) is committed to providing HOPE for people who suffer from devastating nerve and muscle disorders. The only way this can be done is an all out offensive to find a control or cure for such diseases. MDA supports medical and scientific research to the extent that funds will allow, it runs a comprehensive public education programme and provides physical aids, welfare, morale support and counselling to persons in need. The Muscular Dystrophy Association’s programmes are funded, almost entirely, by voluntary contributions from concerned individuals and community organisations.
Following is a list of disorders under the groups mentioned. They are all included in the Muscular Dystrophy Association’s programmes.
1. Disorders of the Voluntary Muscles
Muscular Dystrophies:
* Duchenne Muscular Dystrophy (pseudo-hypertrophic)
* Becker Muscular Dystrophy
* Facioscapulohumeral Muscular Dystrophy (Landouzy-Dejerine)
* Limb-Girdle Muscular Dystrophy (including Juvenile Dystrophy of Erb)
* Ophtalmoplegic Muscular Dystrophy
* Distal Muscular Dystrophy
* Muscular Dystrophy of Late Onset
* Myotonic Dystrophy (Steinert’s Disease)
* Congenital Muscular Dystrophy
Myopathies:
Inflammatory Myopathies:
* Polymyositis
* Dermatomyositis
* Myositis Ossificans
Myotonias:
* Myotonia Congenita (Thomsen’s Disease)
* Paramyotonia Congenita
Metabolic Disease of Muscle:
* Phosphorylase Deficiency (McArdle’s Disease)
* Acid Maltase Deficiency (Pompe’s Disease)
* Phosphofructokinase Deficiency (Tarul’s Disease)
* Debrancher Enzyme Deficiency (Conn’s or Forbe’s Disease)
* Carnitine Deficiency
* Carnitine Palmityltransferase Deficiency
* Periodic Paralysis.
Less Common Myopathies:
* Central Core Disease
* Nemaline Myopathy
* Mitochondrial Disease
* Myotubular Myopathy
* Idiopathic Myopathy
* Malignant Hypertheria (Hyperpyrexia)
2. Disorders of the Motor Neurone
Spinal Muscular Atrophies:
* Motor Neurone Disease
* Infantile Progressive Spinal Muscular Atrophy (Werdnig-Hoffman Disease)
* Juvenile Progressive Muscular Atrophy (Kugelberg-Welander Disease)
* Benign Congenital Hypotonia
* Adult Progressive Spinal Muscular Atrophy (Aran-Duchenne Type)
Diseases of Peripheral Nerve:
* Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease)
* Friedreich’s Ataxia
* Dejerine-Sottas Disease.
3. Disorders of the Nerve - Muscle Junction
Diseases of the Neuromuscular Junction:
* Myasthenia Gravis
* Eaton-Lambert (Myasthenic) Syndrome
* Source : Muscular Dystrophy Association Inc of SA
