Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterised by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified. Myotonic dystrophy type 1 (also known as Steinert's disease) was first described more than 100 years ago, whereas myotonic dystrophy type 2 was identified only 18 years ago, after genetic testing for type 1 disease could be applied. Both diseases are caused by autosomal dominant nucleotide repeat expansions. In patients with myotonic dystrophy type 1, a (CTG)(n) expansion is present in DMPK, whereas in patients with type 2 disease, there is a (CCTG)(n) expansion in CNBP. When transcribed into CUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in a spliceopathy of downstream effector genes. The prevailing paradigm therefore is that both disorders are toxic RNA diseases. However, research indicates several additional pathogenic effects take place with respect to protein translation and turnover. Despite clinical and genetic similarities, myotonic dystrophy type 1 and type 2 are distinct disorders requiring different diagnostic and management strategies.
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