Handbook of Genetic Counseling/Classical Myotonic Dystrophy

Classical Myotonic Dystrophy

What is myotonic dystrophy?
Myotonic dystrophy (DM) is the most common adult form of muscular dystrophy. It is a multisystem disorder that affects the muscles, as well as the eyes, heart, endocrine system, and central nervous system. Myotonic dystrophy causes muscle weakness accompanied by myotonia, a delayed relaxation of muscles after contraction. Myotonic dystrophy, also known as Steinert's disease and dystrophia myotonica, is a hereditary condition. .

What causes myotonic dystrophy?
Myotonic dystrophy is caused by a defect in a gene called DMPK. The gene has a stretch of DNA that contains a series of CTG repeats in its sequence. Normally, the DMPK gene has less than 37 CTG repeats. However, individuals with myotonic dystrophy have more than 37 repeats, making the gene unstable. The greater the number of repeats that an individual has, the more severe the symptoms will be. Genetic anticipation is often observed in the inheritance of myotonic dystrophy. Anticipation means that the number of repeats tends to increase as the disease is passed from one generation to the next, leading to increasing severity of symptoms and decreasing age of onset. Anticipation is most commonly observed in the transmission of myotonic dystrophy from maternal genes.

How does a person get myotonic dystrophy?
Because myotonic dystrophy is a hereditary disorder, it is transmitted from generation to generation. The defective gene is dominant, meaning individuals who inherit the gene from either their mother or their father will have the disorder. If one parent has the disease, there is a 50% chance that myotonic dystrophy will be passed on to their offspring.

What are the symptoms of myotonic dystrophy?
The effects of myotonic dystrophy vary widely, even among members of the same family. Some individuals have symptoms so mild that they hardly notice them. In other individuals, muscle weakness and wasting may cause more severe disabilities. In general, the older a person is when muscle weakness becomes noticeable, the slower the disease progression and the less serious the effects. Myotonic dystrophy is loosely classified into three categories based on the number of CTG repeats in the gene, the severity of the symptoms, and the age of onset. The three forms are: mild, classical, and congenital.

What are the characteristics of classical myotonic dystrophy?
Individuals with classical myotonic dystrophy have 100-1500 CTG repeats in the DMPK gene. The age of onset is typically between 10 and 30 years. The predominant symptom is muscle weakness and wasting which usually begins in the distal limb muscles, including the forearms, hands, feet, and ankles. This muscle weakening may lead to foot drop and difficulty performing tasks requiring hand dexterity. Muscle weakening may also be observed in the neck or shoulders. Very rarely, the disease may progress to the point where an individual is confined to a wheel chair. Myotonia is also observed and may lead to difficulty performing some daily activities. Individuals with myotonic dystrophy often have long, thin faces, and weakness of the muscles in the eyelids may cause them to droop. Some men with myotonic dystrophy experience frontal balding. Other symptoms that individuals may experience include speech problems, cataracts, and cardiac arrhythmia. Myotonic dystrophy may also lead to constipation, diarrhea, or gallstones. In the later stages of the disease, some people experience sleep apnea and hypersomnia. Women with myotonic dystrophy have an increased risk for pregnancy complications. Problems may include an increased risk for spontaneous abortions, prolonged labor, a retained placenta, and post partum hemorrhaging. Men may experience testicular atrophy, although myotonic dystrophy has not been associated with an increase in infertility. Hyperinsulinism and abnormalities in the secretion of growth hormones have also been observed, but they rarely cause clinical problems. Learning problems have been associated with classical myotonic dystrophy. Also, obsessive compulsive, passive-aggressive, and avoidant behaviors have all been observed in some individuals with the condition. Individuals with myotonic dystrophy may have a shortened life span. The average age of death is 48-55 years old. Common causes of death include pneumonia, respiratory failure, cardiovascular problems, sudden death arrhythmia, and tumors.

How is myotonic dystrophy diagnosed?
A physical examination may reveal muscle weakness and myotonia. A special test called a muscle biopsy can confirm the diagnosis. Also, DNA testing can be performed to determine the number of CTG repeats on the DMPK gene. This blood test is 100% sensitive and specific. Presymptomatic testing is available for individuals who have no features of the condition but have a family history of myotonic dystrophy. Prenatal testing is also available.

How is myotonic dystrophy treated/managed?
Currently, there is no treatment for myotonic dystrophy. Muscle weakness can be managed with orthotics or other assistive devices. Treatment is available for many symptoms of myotonic dystrophy, including cataracts, diabetes, hypothyroidism, sleep apnea, and myotonia. In addition, close monitoring of the heart with an annual EKG, the eyes with an annual ophthalmologic exam, and screens for glucose concentration can provide early identification of some potential effects of myotonic dystrophy.

What informational and support resources are available?

 * Muscular Dystrophy Association
 * 3300 East Sunrise Drive
 * Tucson, AZ 85718-3208
 * (800) 572-1717
 * Email: mda@mdausa.org
 * [Web: http://www.mdausa.org/]


 * Myotonic Dystrophy Website
 * [www.umd.necker.fr/myotonic_dystrophy.html]


 * NCBI Genes and Disease Webpage
 * [www.ncbi.nim.nig.gov/disease/Myotonic.html]