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.
CNBP (ZNF9) is the only gene known to be associated with 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 assay."
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 gene expansion; de novo mutations 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 50% risk is possible when the presence of a CNBP expansion has been identified in the affected parent.