Myotonic dystrophy types 1 and 2.

Myotonic dystrophies (dystrophia myotonica, or DM) are inherited disorders characterized by myotonia and progressive muscle degeneration, which are variably associated with a multisystemic phenotype. To date, two types of myotonic dystrophy, type 1 (DM1) and type 2 (DM2), are known to exist; both are autosomal dominant disorders caused by expansion of an untranslated short tandem repeat DNA sequence (CTG)(n) and (CCTG)(n), respectively. These expanded repeats in DM1 and DM2 show different patterns of repeat-size instability. Phenotypes of DM1 and DM2 are similar but there are some important differences, most conspicuously in the severity of the disease (including the presence or absence of the congenital form), muscles primarily affected (distal versus proximal), involved muscle fiber types (type 1 versus type 2 fibers), and some associated multisystemic phenotypes. The pathogenic mechanism of DM1 and DM2 is thought to be mediated by the mutant RNA transcripts containing expanded CUG and CCUG repeats. Strong evidence supports the hypothesis that sequestration of muscle-blind like (MBNL) proteins by these expanded repeats leads to misregulated splicing of many gene transcripts in corroboration with the raised level of CUG-binding protein 1. However, additional mechanisms, such as changes in the chromatin structure involving CTCN-binding site and gene expression dysregulations, are emerging. Although treatment of DM1 and DM2 is currently limited to supportive therapies, new therapeutic approaches based on pathogenic mechanisms may become feasible in the near future.