Myotonic dystrophy

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Myotonic dystrophy is the most common form of muscular dystrophy in adults, with a prevalence of 1 in 8,000. It is a slowly progressive, multi-system disorder that affects skeletal muscles, the heart, gastrointestinal smooth muscle, uterine smooth muscle, the eyes, and the endocrine and central nervous systems. Myotonic dystrophy is almost always caused by an autosomal dominant gene mutation in the DMPK gene located on chromosome 19. The gene mutation is an expansion in the length of a three base-pair (triplet) repeat sequence (cytosine–thymine–guanine, or CTG) above the normal upper limit of 35 repeats. The expanded CTG repeat is classed as a ‘dynamic’ mutation because the number of repeats tends to increase in size over successive generations in myotonic dystrophy families. In general, larger CTG expansions are associated with earlier age-of-onset and more severe signs and symptoms of myotonic dystrophy. Patients with 50–100 CTG repeats may develop cataract, diabetes, grip myotonia, or mild muscle weakness in mid to late adulthood. Patients with 200–500 CTG repeats are affected earlier and more severely by facial and distal limb muscle weakness and myotonia. A CTG repeat size above 1,000 is associated with prenatal onset of disease and congenital myotonic dystrophy, which may be fatal due to respiratory failure. Feeding difficulties, muscle weakness, club foot deformity, and cognitive impairments are present in surviving infants. Although males and females are equally likely to inherit myotonic dystrophy, the very large mutations (>1,000 repeats) which result in the congenital form of myotonic dystrophy are virtually always transmitted by an affected mother. DNA tests are used to estimate repeat size and permit accurate prenatal, presymptomatic, and diagnostic genetic testing.