Myotonic Dystrophies: A Genetic Overview

Abstract

Myotonic dystrophies (DM) are the most common muscular dystrophies in adults, which can affect other non-skeletal muscle organs such as the heart, brain and gastrointestinal system. There are two genetically distinct types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), both dominantly inherited with significant overlap in clinical manifestations. DM1 results from CTG repeat expansions in the 3′-untranslated region (3′UTR) of the DMPK (dystrophia myotonica protein kinase) gene on chromosome 19, while DM2 is caused by CCTG repeat expansions in intron 1 of the CNBP (cellular nucleic acid-binding protein) gene on chromosome 3. Recent advances in genetics and molecular biology, especially in the field of RNA biology, have allowed better understanding of the potential pathomechanisms involved in DM. In this review article, core clinical features and genetics of DM are presented followed by a discussion on the current postulated pathomechanisms and therapeutic approaches used in DM, including the ones currently in human clinical trial phase.