Myotonic Dystrophies

Abstract

Myotonic dystrophies (DM) are the most common muscular dystrophies in adults. They include myotonic dystrophy type 1 (DM1) or Steinert’s disease, and myotonic dystrophy type 2 (DM2), formerly known as proximal myotonic myopathy (PROMM). DM1 and DM2 are autosomal dominant disorders characterized by variable age of onset, a slowly progressive muscle weakness associated with a varying degree of clinical and electrical myotonia, and a wide range of extramuscular manifestations. Similarities between the genetic defects in these two disorders likely underlie many shared phenotypic features of DM1 and DM2: indeed, both diseases are caused by pathological expansions of polymorphic short DNA tandem repeats, located in non-coding sequences of their respective genes, dystrophia myotonica protein kinase (DMPK) in DM1 and cellular nucleic acid-binding protein (CNBP), also named zinc finger protein 9 (ZNF9) in DM2. Both repeat expansions lead to aberrant splicing of mRNA of several extramuscular genes, which is the basis of the multisystem phenotypes of these disorders. This chapter summarizes the main clinical and molecular features of DM1 and DM2 and provides an update regarding their pathogenesis, clinical and diagnostic management, current and future therapeutic perspectives, also highlighting unsolved challenges in the management of these disorders.