Myotonic Dystrophy: Sum and Substance

Myotonic dystrophy is an autosomal dominant, multisystem disorder that is characterized by myotonic myopathy. The unstable repeat expansions of (CTG)n repeat in the 3'-UTR of the DMPK gene and a (CCTG)n repeat in intron 1 of the CNBP (formerly ZNF9) gene cause the two known subtypes of myotonic dystrophy: (i) Myotonic Dystrophy type 1 (DM1) and (ii) Myotonic Dystrophy type 2 (DM2) respectively. This review will focus on the molecular pathophysiology, genetics, diagnosis, management and therapeutics aspect of myotonic dystrophy. The length of the (CTG)n repeat expansion in DM1 correlates with disease severity and age of onset. The symptoms and severity of Myotonic Dystrophy Type 1 (DM1) ranges from severe and congenital forms. In adult patients, cardiac conduction abnormalities may occur and cause a shorter life span. In subsequent generations, the symptoms in DM1 may present at an earlier age and have a more severe course (anticipation). In Myotonic Dystrophy Type 2 (DM2), no anticipation is described, but cardiac conduction abnormalities as in DM1 are observed and patients with DM2 additionally have muscle pain and stiffness. Because of the disease characteristics in DM1 and DM2, appropriate molecular testing and reporting are very important for the optimal counselling in myotonic dystrophy. There is currently no cure but supportive management helps equally to reduce the morbidity and mortality and patients need close follow up to pay attention to their clinical problems.