Myotonic syndromes

Purpose of review To highlight recent advances in understanding the clinical manifestations and molecular genetics of myotonic syndromes, with particular emphasis on the myotonic dystrophies. Recent findings Myotonic syndromes include the non-dystrophic myotonias, caused by mutations in genes encoding the chloride or sodium channels that are specific to skeletal muscle, and the myotonic dystrophies. Previous studies have shown that myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the DMPK gene. Recently, it was discovered that myotonic dystrophy type 2 (proximal myotonic myopathy) is also caused by a DNA expansion mutation. In both types of myotonic dystrophy the expanded repeat is transcribed and the RNA produced from the mutant allele is retained in nuclear inclusions. Recent studies suggest that the mutant RNA has a toxic effect on muscle fibers by interfering with the essential functions of the myonucleus, such as RNA processing. Summary It now appears likely that myotonic dystrophy is the first instance of a genetic disease in which the harmful effect of a mutation involves the production of a pathogenic RNA. However, the exact mechanism is not understood, and it is unclear whether this RNA-mediated disease process is also responsible for the manifestations of myotonic dystrophy in non-muscle tissues.