Muscular Dystrophy Health Article

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 a 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 a very small number of female carriers.
• Becker muscular dystrophy (BMD). BMD affects older boys and young men, following a milder course than DMD. BMD occurs in about one in 30,000 male births.
• Emery-Dreifuss muscular dystrophy (EDMD). EDMD can appear as an autosomal dominant or recessive form of dystrophy. Thus, both young boys and girls can be affected. It causes 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 and also the muscles of the arms and legs. It is the most variable of the muscular dystrophies, and there are several different forms of the condition now recognized. Many people with suspected LGMD have probably been misdiagnosed in the past, and therefore the prevalence of the condition is difficult to estimate. The highest prevalence of LGMD is in a small mountainous Basque province in northern Spain, where the condition affects 69 persons per million.
• Facioscapulohumeral muscular dystrophy (FSH). FSH, also known as Landouzy-Dejerine condition, 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 one out of every 20,000 people, and affects approximately 13,000 people in the United States.
• Myotonic dystrophy. This is also known as Steinert's disease and affects both men and women, causing generalized weakness first seen in the face, feet, and hands. Other systems of the body can also be affected. 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 genders, 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 is a group of rare muscle diseases that have in common weakness and wasting of the distal (farthest from the center) muscles of the forearms, hands, lower legs, and feet. In general, the DDs are less severe, progress more slowly, and involve fewer muscles than the other dystrophies. DD usually 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 a rare group of muscular dystrophies that have in common the presence of muscle weakness at birth (congenital). Biopsies of muscles from persons affected with CMD are abnormal. CMD results in generalized weakness, and usually progresses slowly. A subtype, called Fukuyama CMD, also involves mental retardation and lissencephaly. It is more common in Japan.

The muscular dystrophies are genetic conditions, meaning they are caused by alterations 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 conditions to occur, both copies must be altered. Such conditions are called autosomal recessive conditions. Some forms of LGMD, OPMD and DD exhibit this pattern of inheritance, as does CMD. Persons with only one altered copy, called carriers, will not have the condition, but may pass the altered gene on to their children. When two carriers have children, the chances of having a child with the condition is one in four for each pregnancy.

Other conditions occur when only one altered gene copy is present. Such conditions are called autosomal dominant conditions. Other forms of LGMD exhibit this pattern of inheritance, as do DM, FSH, OPMD, and some forms of DD. When a person affected by the condition has a child with someone not affected, the chances of having an affected child are one in two. Autosomal dominant conditions tend to be variable in their symptoms even among members of the same family.

Because of chromosomal differences between the genders, some genes are not present in two copies. The chromosomes that determine whether a person is male or female are called the X and Y chromosomes. A person with two X chromosomes is female, while a person with one X and one Y is male. While the X chromosome carries many genes, the Y chromosome carries almost none. Therefore, a male has only one copy of each gene on the X chromosome, and if it is altered, he will have the condition that alteration causes. Such conditions are said to be X-linked. X-linked conditions include DMD, BMD, and EDMD. Women are not usually affected by X-linked conditions, since they will likely have one unaltered copy between the two chromosomes. Some female carriers of DMD have a mild form of the condition, probably because their one unaltered gene copy is shut down in some of their cells.

Women carriers of X-linked conditions have a one in two chance of passing the altered gene on to each child born. Daughters who inherit the altered gene will be carriers. A son born without the altered gene will be free of the condition and cannot pass it on to his children. A son born with the altered gene will have the condition. He will pass the altered gene on to each of his daughters, who will then be carriers, but to none of his sons (because they inherit his Y chromosome).

Not all genetic alterations are inherited. As many as one-third of the cases of DMD are due to new mutations that arise during egg formation in the mother. New mutations are less common in other forms of muscular dystrophy.