Myotonic dystrophy: disease repeat range, penetrance, age of onset, and relationship between repeat size and phenotypes

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease primarily characterized by myotonia and progressive muscle weakness. The pathogenesis of DM involves microsatellite expansions in noncoding regions of transcripts that result in toxic RNA gain-of-function. Each successive generation of DM families carries larger repeat expansions, leading to an earlier age of onset with increasing disease severity. At present, diagnosis of DM is challenging and requires special genetic testing to account for somatic mosaicism and meiotic instability. While progress in genetic testing has been made, more rapid, accurate, and cost-effective approaches for measuring repeat lengths are needed to establish clear correlations between repeat size and disease phenotypes.