Myotonic Dystrophy


BACKGROUND:

Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy. It is an autosomal dominant disorder with an incidence of about 1:8000 individuals. Clinical expression is highly variable and features muscle weakness and atrophy, evidence of myotonia, cataracts, intellectual impairment, cardiac conduction defects, testicular atrophy in males and premature balding. The disease commonly demonstrates "anticipation", that is, successive generations in families affected with myotonic dystrophy show earlier onset and greater severity of symptoms. The molecular basis of anticipation is expansion of a CTG triplet repeat in the DM kinase gene. Normal alleles have between 5 and 40 CTG repeats. Individuals with greater than 40 CTG repeats (up to several thousand) are affected. An increase in the length of the CTG repeat sequence in successive generations parallels an increase in clinical severity, culminating in congenital disease in patients with several thousand CTG repeats, particularly when transmitted by an affected mother.

INDICATIONS FOR TESTING:

  • Confirmation of a clinical diagnosis of myotonic dystrophy.

  • Presymptomatic screening in individuals with a family history of DM.

  • Prenatal testing for DM.

SAMPLE REQUIREMENTS:

Blood: Two 5 ml purple-top (EDTA) vacutainers of whole blood inverted several times to mix. Forward within 48 hours at room temperature.

Amniotic Fluid: 10-15 ml amniotic fluid during 14th - 17th week of gestation. Send specimen refrigerated, but not frozen (do not ship on dry ice). Please use an overnight courier service.

INTERPRETATION:

The number of CTG repeats is determined by PCR and Southern blot assays. Individuals with less than 40 CTG repeats are normal. Affected individuals have DM gene expansions consisting of greater than 40 to several thousand CTG repeats. Those with small expansions (40 to 200 CTG repeats) generally have very mild symptoms including cataracts or premature frontal baldness. Moderate expansions (200 to 600 CTG repeats) result in late onset muscle disease, whereas large expansions (up to several thousand CTG repeats) can cause severe symptoms with congenital onset.

COUNSELING ISSUES:

  1. Exact prediction of prognosis cannot be made from CTG repeat size determination alone. The general correlation between CTG repeat length and severity of clinical symptoms cited above contains considerable overlap among different size classes and should be interpreted with caution.

  2. A few patients have been identified with classical clinical features including electromyographic findings and no evidence of CTG repeat expansion. Therefore, documentation of CTG repeat expansion in an affected family member is recommended prior to testing of at risk individuals.

 

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