Muscular dystrophy

Encyclopedia of Medicine by Richard Robinson

Definition

Muscular dystrophy is the name for a group of inherited disorders in which strength and muscle bulk gradually decline. Nine types of muscular dystrophies are generally recognized.

Description

The muscular dystrophies include:

• Duchenne muscular dystrophy (DMD): DMD affects young boys, causing progressive muscle weakness, usually beginning in the legs. It is the most severe form of muscular dystrophy. DMD occurs in about 1 in 3,500 male births, and affects approximately 8,000 boys and young men in the United States. A milder form occurs in very few female carriers.
• Becker muscular dystrophy (BMD): BMD affects older boys and young men, following a milder course than DMD. BMD occurs in about 1 in 30,000 male births.
• Emery-Dreifuss muscular dystrophy (EDMD): EDMD affects young boys, causing contractures and weakness in the calves, weakness in the shoulders and upper arms, and problems in the way electrical impulses travel through the heart to make it beat (heart conduction defects). Fewer than 300 cases of EDMD have been identified.
• Limb-girdle muscular dystrophy (LGMD): LGMD begins in late childhood to early adulthood and affects both men and women, causing weakness in the muscles around the hips and shoulders. It is the most variable of the muscular dystrophies, and there are several different forms of the disease now recognized. Many people with suspected LGMD have probably been misdiagnosed in the past, and therefore the prevalence of the disease is difficult to estimate. The number of people affected in the United States may be in the low thousands.
• Facioscapulohumeral muscular dystrophy (FSH): FSH, also known as Landouzy-Dejerine disease, begins in late childhood to early adulthood and affects both men and women, causing weakness in the muscles of the face, shoulders, and upper arms. The hips and legs may also be affected. FSH occurs in about 1 out of every 20,000 people, and affects approximately 13,000 people in the United States.
• Myotonic dystrophy: also known as Steinert's disease, affects both men and women, causing generalized weakness first seen in the face, feet, and hands. It is accompanied by the inability to relax the affected muscles (myotonia). Symptoms may begin from birth through adulthood. It is the most common form of muscular dystrophy, affecting more than 30,000 people in the United States.
• Oculopharyngeal muscular dystrophy (OPMD): OPMD affects adults of both sexes, causing weakness in the eye muscles and throat. It is most common among French Canadian families in Quebec, and in Spanish-American families in the southwestern United States.
• Distal muscular dystrophy (DD): DD begins in middle age or later, causing weakness in the muscles of the feet and hands. It is most common in Sweden, and rare in other parts of the world.
• Congenital muscular dystrophy (CMD): CMD is present from birth, results in generalized weakness, and usually progresses slowly. A subtype, called Fukuyama CMD, also involves mental retardation. Both are rare; Fukuyama CMD is more common in Japan.

Causes & symptoms

Causes

Several of the muscular dystrophies, including DMD, BMD, CMD, and most forms of LGMD, are due to defects in the genes for a complex of muscle proteins. This complex spans the muscle cell membrane to unite a fibrous network on the interior of the cell with a fibrous network on the outside. Current theory holds that by linking these two networks, the complex acts as a "shock absorber," redistributing and evening out the forces generated by contraction of the muscle, thereby preventing rupture of the muscle membrane. Defects in the proteins of the complex lead to deterioration of the muscle. Symptoms of these diseases set in as the muscle gradually exhausts its ability to repair itself. Both DMD and BMD are caused by flaws in the gene for the protein called dystrophin. The flaw leading to DMD prevents the formation of any dystrophin, while that of BMD allows some protein to be made, accounting for the differences in severity and onset between the two diseases. Differences among the other diseases in the muscles involved and the ages of onset are less easily explained.

The causes of the other muscular dystrophies are not as well understood:

• One form of LGMD is caused by defects in the gene for a muscle enzyme, calpain. The relationship between this defect and the symptoms of the disease is unclear.
• EDMD is due to a defect in the gene for a protein called emerin, which is found in the membrane of a cell's nucleus, but whose exact function is unknown.
• Myotonic dystrophy is linked to gene defects for a protein that may control the flow of charged particles within muscle cells. This gene defect is called a triple repeat, meaning it contains extra triplets of DNA code. It is possible that this mutation affects nearby genes as well, and that the widespread symptoms of myotonic dystrophy are due to a range of genetic disruptions.
• The gene for OPMD appears to also be mutated with a triple repeat. The function of the affected protein may involve translation of genetic messages in a cell's nucleus.
• The cause of FSH is unknown. Although the genetic region responsible for it has been localized on its chromosome, the identity and function of the gene or genes involved had not been determined as of 1997.
• The gene responsible for DD has not yet been found.

Genetics and patterns of inheritance

The muscular dystrophies are genetic diseases, meaning they are caused by defects in genes. Genes, which are linked together on chromosomes, have two functions: They code for the production of proteins, and they are the material of inheritance. Parents pass along genes to their children, providing them with a complete set of instructions for making their own proteins.

Because both parents contribute genetic material to their offspring, each child carries two copies of almost every gene, one from each parent. For some diseases to occur, both copies must be flawed. Such diseases are called autosomal recessive diseases. Some forms of LGMD and DD exhibit this pattern of inheritance, as does CMD. A person with only one flawed copy, called a carrier, will not have the disease, but may pass the flawed gene on to his children. When two carriers have children, the chances of having a child with the disease is one in four for each pregnancy.