Muscular Dystrophies

Muscular Dystrophies

Muscular Dystrophy is an umbrella term used it indicate a group of progressive, genetically determined disorders of skeletal and sometimes cardiac muscles which are all very rare. The main feature they have in common is a loss of muscular tissue leading to an increasing weakness of the affected limbs. The severity of this weakness determines the prognosis of the disease and differs greatly in the various forms of dystrophies. These different forms, all named after the first describer, can be distinguished by three characteristics: mode of inheritance (X-linked recessive, autosomal recessive and autosomal dominant), the age of onset and the group of muscles where the disease starts.

As yet research has failed to explain the exact mechanism of the degeneration of muscular fibers. In some forms there seems to be a lack of a certain protein, called dysthrophin, which is part of the healthy muscular cell membrane.

The clinical features for the disease differ a lot. In most forms the infant appears healthy at birth and during early childhood. The first symptom is normally a mild weakness and a loss of muscle tissue, which is replaced by fat. All forms are progressive, which means that the disease is getting worse in the course of time, very rapidly in some forms and relatively slowly in others.

In the most severe forms the patient becomes more and more disabled and immobile and the useless muscles become contracted, which is very painful and fixes the joints in a bend position, thus disabling the patient even further. Eventually the disease reaches the breathing muscles, which leads to complications like chest infections and heart disease and in most cases is the ultimate cause of death.

Since the weakness affects certain groups of muscles in a pattern typical to this disorder, there are clinical signs, which are seen in many patients suffering from one of the more common forms:

Trendelburg Gait: While walking the pelvis can not be kept horizontal and therefore swings from one side to the other. Gowers Sign: If sitting, the child has difficulties in rising to an erect position, climbing up his own legs with his hands to stand up. Pseudohypertrophy of the calves: Due to wasting of the thigh muscles the calves, which are not affected by the disease, appear much too big in comparison.

Scapula Alata: In the advanced stage with progression of the dystrophy to the trunk both scapulae lift off the ribcage due to muscular weakness. In most cases the presentation is so typical that the diagnosis can be made without any further test. In most forms the walking is impaired very early on and the patient shows a very typical gait. Mainly the mild forms with late onset and very slow progression cause problems and require invasive investigations to confirm the muscular dystrophy. A blood test is available, which detects an enzyme (creatin phosinaquse) specific for the muscle that is grossly elevated in people suffering from muscular dystrophy. Even more exact results are obtained if a muscle biopsy is performed, which means a very small piece of muscle is taken out and closely examined under a microscope.

The most advanced technique is the DNA analysis, which can be done from a simple blood sample, but is only available for the Duchenne type. The main use of this test is to determine the carrier status of relatives of an affected person. There are three possibilities for every family member: Sufferer: They do have the faulty gene and suffer from the disease. Carrier: Even though they carry the gene that determines the disease they do not show any symptoms and have a normal live expectancy, but they can inherit the disease to the next generation.

Non-Carrier: Those family members who have two sets of healthy genes and therefore neither suffer from the disease nor can inherit it. So far there is no curative treatment for the disease available, so the main goal is to preserve mobility as long as possible and to prevent early contractions. This is achieved by intensive passive physiotherapy and the adequate use of supportive means like walking sticks, frames or wheelchair. In later stages, when walking has become impossible and contractions make the use of a wheelchair difficult, minor surgery can be used to make passive movement of a joint possible by cutting the shortened tendons. In the severe forms leading to an early death due to respiratory failure the use of oxygen support, first part time and then continuously, is indicated. The cardiac difficulties associated with some kinds of muscular dystrophy may require treatment with a pacemaker. Sometimes also drugs are used to obtain relief. These measures do not reverse the disease, but they may improve the quality of life for the victim.

A very important part of the treatment in the malignant forms is psychological counseling for the patient to help him come to terms with this extremely disabling disease and the inevitable death and to prepare the patient to take part in important medical decisions, e.g. surgical intervention, life prolonging therapy e.t.a.

Lastly there is the genetic counseling for close relatives. For the mother of a boy with Duchenne muscular dystrophy the risk for every male baby to be affected is 50%, the same is the case for sisters of a patient if they are a carrier of the gene. Even though in most countries the selective abortion of a male fetus is legal, most carrier females decide against any further pregnancies.

As mentioned in the in the first part of my paper the different kinds of muscular dystrophies differ in the mode of inheritance: X-linked recessive, autosomal recessive and autosomal dominant.

In the group of X-linked disorders exist two different forms. Firstly the malignant Duchenne Muscular Dystrophy, which is actually the most common form of all Muscular Dystrophies wi th and an incidence of 1 in 3000 male infants and the only one so far for which DNA testing is possible. The first symptoms normally occur between the first and third year, affecting the pelvic and thigh muscles first. The disease progresses very rapidly with an increasing weakness in the legs and spreading to the arm and trunk, often affecting the heartmuscles as well. In most cases the boy is severely disabled by the age of 10 and only very few reach the age of 20. The Duchenne Muscular Dystrophy is the only form, which only occurs in male infants because the patient himself is infertile. For this reason the path of inheritance always follows the maternal line. The other form is the Becker-Kiener Muscular Dystrophy, which is benign. Patients become symptomatic during childhood or adolescents (year 6-19) with initial weakness in the pelvic and the thigh muscles, as in the Duchenne form. The progression is slow, and even though the life expectancy is 10-20 years less than in the average population, the patient has in most cases a good mobility for the best part of life. The vast majority of sufferers is male, females can only be sufferers if a male patient has a partner who is also carrier of the gene, e.g. a relative. The group of autosomal recessive disorders also consists of a malignant and a benign form. The De Lange Muscular Dystrophy is the only form of the disease that is already present at birth. The mother often reports a lack of child movements during late pregnancy and the newborn baby presents as a 'floppy' infant. This form is the most progressive as well, in most cases causing a very early death before the first birthday. The Leyden-Möbius Muscular Dystrophy becomes apparent during adolescent (year 10-20), affecting the upper arm and pelvic muscles equally, which gave it the name limb girdle dystrophy. The progression is slow and the course of the disease and the prognosis similar to the Becker-Kiener type (above). This form occurs in males and females with the same frequency. As in all autosomal recessive disorders the risk is especially high for people who marry a family member. In the last group, which is described by the autosomal dominant mode of inheritance exists a large number of very rare forms. They all show a very mild progression and affect only a limited group of muscles, mostly those in the face, the upper back and the shoulders, which gave them the name facio-scapulo-humeral dystrophies. The age of onset varies between adolescents (years10-20) and late adulthood (years 40-60), depending on the type. Less common is an involvement of the eye and pharynx muscles, leading to a dropping eyelid, vision disturbance (e.g. double vision) and problems with swallowing.

The prognosis for all these forms is equally good with a normal life expectancy in most cases and only mild muscular weakness.

Works Cited

"Muscular Dystrophy." The American Medical Association: Encyclopedia of Medicine. New York: Random House, 1989.

"Muscular Dystrophy." The American Medical Association: Family Medical Guide. 3rded. New York: Random House, 1994.

"Muscular Dystrophy." The new good housekeeping family health and medical guide. 10thed. New York: Hearst Books, 1989. Weatherall D.J., Ledingham J.G.G., and Warrell D.A., eds . Oxford Textbook of Medicine. Vol. 2. Oxford: Oxford UP, 1987. 2vols. West Virginia Health Page. Types of Muscular Dystrophy. Online. U. of West Virginia. Internet. 22 Sep. 1998. Available

:http://www.wvhealth.wvu.edu/Neurological/musctype.htm