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Myotonic Dystrophy Type 2.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2006 Sep 21 [updated 2013 Jul 3].

Author information

1
Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, Genetic Counselor, Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota, Minneapolis, Minnesota
2
Director, Center for NeuroGenetics, Professor, Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida
3
Director, Neuromuscular Division and Clinics, Department of Neurology, Stanford University, Stanford, California

Excerpt

CLINICAL CHARACTERISTICS:

Myotonic dystrophy type 2 (DM2) is characterized by myotonia (90% of affected individuals) and muscle dysfunction (weakness, pain, and stiffness) (82%), and less commonly by cardiac conduction defects, iridescent posterior subcapsular cataracts, insulin-insensitive type 2 diabetes mellitus, and testicular failure. Although myotonia (involuntary muscle contraction with delayed relaxation) has been reported during the first decade, onset is typically in the third decade, most commonly with fluctuating or episodic muscle pain that can be debilitating and weakness of the neck flexors and finger flexors. Subsequently, weakness occurs in the elbow extensors and the hip flexors and extensors. Facial weakness and weakness of the ankle dorsiflexors are less common. Myotonia rarely causes severe symptoms.

DIAGNOSIS/TESTING:

CNBP (ZNF9) is the only gene in which pathogenic variants are known to cause myotonic dystrophy type 2. CNBP intron 1 contains a complex repeat motif, (TG)n(TCTG)n(CCTG)n. Expansion of the CCTG repeat causes DM2. The number of CCTG repeats in expanded alleles ranges from approximately 75 to more than 11,000, with a mean of approximately 5000 repeats. The detection rate of a CNBP CCTG expansion is more than 99% with the combination of routine PCR, Southern blot analysis, and the PCR repeat-primed assay.

MANAGEMENT:

Treatment of manifestations: Ankle-foot orthoses, wheelchairs, or other assistive devices as needed for weakness; defibrillator placement for those with arrhythmias; removal of cataracts that impair vision; and testosterone replacement therapy for hypogonadism in males. Myotonia rarely requires treatment. Routine physical activity appears to help maintain muscle strength and endurance and to control musculoskeletal pain. Medications used with some success in pain management include mexilitene, gabapentin, nonsteroidal anti-inflammatory drugs (NSAIDS), low-dose thyroid replacement, low-dose steroids (e.g., 5 mg prednisone on alternate days), and tricyclic antidepressants. Prevention of secondary complications: Anesthetic risk may be increased and therefore assessment of cardiac and respiratory function before and after surgery are recommended. Prompt treatment of hypothyroidism to reduce secondary weakness. Surveillance: Annual ECG and echocardiogram or possible cardiac MRI to detect/monitor cardiac conduction defects and cardiomyopathy; annual measurement of fasting serum glucose concentration and glycosylated hemoglobin level; and testing of males every few years for evidence of hypogonadism. Agents/circumstances to avoid: Cholesterol-lowering medications when associated with increased weakness.

GENETIC COUNSELING:

Myotonic dystrophy type 2 is inherited in an autosomal dominant manner. To date, all individuals whose biological parents have been evaluated with molecular genetic testing have had one parent with a CNBP expansion; de novo pathogenic variants have not been reported. Each child of an individual with a CNBP expansion has a 50% chance of inheriting the expansion. Neither the size of a predominant allele nor the total number of different detectable expansions in a single sample can predict disease severity, age of onset, or clinical symptoms. Prenatal testing for pregnancies at increased risk is possible if the presence of a CNBP expansion has been identified in the affected parent.

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