Myotonic dystrophy

Myotonic dystrophy is an inherited disorder of the muscles and other body systems. It is the most common form of muscular dystrophy that begins in adulthood.

This disorder is characterized by progressive muscle wasting and weakness, particularly in the lower legs, hands, neck, and face. People with myotonic dystrophy often have prolonged muscle tensing (myotonia) and are not able to relax certain muscles after use. For example, a person may be unable to release a grip on a doorknob or handle.

Other signs and symptoms of myotonic dystrophy include clouding of the lens of the eye (cataracts) and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). In affected men, hormonal changes may lead to balding and an inability to father a child (infertility). The features of this disorder usually develop during a person's twenties or thirties, although they can occur at any age. The severity of the condition varies widely among affected people, even among members of the same family.

The two types of myotonic dystrophy are designated type 1 and type 2. The clinical features of type 2 myotonic dystrophy tend to be milder than those of type 1, and the two types are caused by mutations in different genes.

A variation of type 1 myotonic dystrophy, called congenital myotonic dystrophy, can be noted at birth. The signs and symptoms include generalized weakness, weak muscle tone (hypotonia), club foot, breathing problems, developmental delays, and intellectual disability. In some cases, these medical problems are severe or life-threatening.

Myotonic dystrophy affects about 1 in 8,000 people worldwide. Type 1 is the most common form of the condition, accounting for about 98 percent of all cases. The remaining 2 percent of cases are myotonic dystrophy, type 2. The prevalence of the two types of myotonic dystrophy varies among different ethnic populations. For example, among people with German ancestry, type 2 may be as common as type 1.

Myotonic dystrophy type 1 is caused by a mutation in the DMPK gene, while a mutation in the CNBP gene is responsible for the less common myotonic dystrophy type 2. The exact function of these genes is not known. The DMPK gene may play a role in communication within cells and appears to be important for the correct functioning of cells in the heart, brain, and muscles used for movement (skeletal muscles). The protein made by the CNBP gene is primarily found in the heart and in skeletal muscles, where it probably helps regulate the function of other genes.

Similar mutations in the DMPK and CNBP genes cause the two forms of myotonic dystrophy. In each case, a short segment of DNA is abnormally repeated many times, forming an unstable region in the gene. The mutated gene produces an altered version of messenger RNA, which is a molecular blueprint of the gene that is normally used for protein production. The abnormal messenger RNA forms clumps inside the cell that interfere with the production of many proteins. These changes prevent cells in muscles and other tissues from functioning normally, leading to the signs and symptoms of myotonic dystrophy.

Read more about the CNBP and DMPK genes.

Both types of myotonic dystrophy are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one affected parent.

As myotonic dystrophy is passed from one generation to the next, the disorder generally begins earlier in life and signs and symptoms become more severe. This phenomenon is called anticipation. In type 1 myotonic dystrophy, anticipation is caused by an increase in the length of the unstable region in the DMPK gene. In type 2 myotonic dystrophy, a longer unstable region in the CNBP gene does not appear to influence the age of onset of the disorder. The cause of the anticipation observed in families with type 2 myotonic dystrophy is unknown.