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Muscular dystrophy (MD) was originally defined as a single disease in the 19th century. In the 20th century, MD was delineated into the following 6 subcategories: Duchenne MD (DMD)/Becker MD, limb-girdle MD, distal myopathies, congenital MD, facioscapulohumeral MD, and myotonic dystrophy. Since the cloning of dystrophin in 1986, a flood of genetic discoveries has made it apparent that muscular dystrophy actually refers to a superfamily of more than 50 distinct diseases definable by specific genetic mutations. Thus, this term is rapidly becoming an anachronism that is likely to be replaced by specific molecular diagnoses. Adding to the complexity, many causative genes are associated with multiple phenotypes, such as the link between dysferlin and both Miyoshi myopathy and limb-girdle MD 2B. However, specific genotype-phenotype associations still provide guidance regarding which genes are likely to harbor pathogenic mutations. Whole-exome sequencing and whole-genome sequencing are becoming widely available diagnostic tools. Moreover, new diseases continue to be identified by whole-exome sequencing and whole-genome sequencing, some of which are exceedingly rare but have important mechanistic and therapeutic connections to other MDs. Diagnosis is further complicated by the clinical overlap between MDs and other inherited myopathies, illustrated by our work on MEGF10 myopathy.1 Whole-exome sequencing, whole-genome sequencing, and sophisticated bioinformatic strategies also promise to identify genes, such as LTBP4 in DMD, that modify the course or treatment responses of these mendelian disorders.2
Kang PB, Griggs RC. Advances in Muscular Dystrophies. JAMA Neurol. 2015;72(7):741-742. doi:10.1001/jamaneurol.2014.4621