Dysferlinopathy encompasses several clinical entities, having in common a deficit in dysferlin, a protein involved in muscle fibre membrane repair mechanisms. Initially reduced simply to Myoshi distal myopathy, the phenotype spectrum was rapidly extended to pure proximal forms such as limb-girdle muscular dystrophy (LGMD) R2, and especially to mixed proximal/distal forms. Dysferlinopathy is transmitted in an autosomal recessive manner and is slow-progressing, and with the support of the American Jain Foundation, it is currently the subject of a highly ambitious disease natural history study with a view to future therapeutic trials, called the Jain COS (Jain Clinical Outcome Study). This is an opportunity for the investigators to clarify the phenotype differences between these different clinical entities.
In an article published in 2021, the international consortium reviewed the clinical, laboratory and muscle imaging data of the different phenotypes into which the 168 patients participating in the protocol were classified. It reached the conclusion that, in fact, this involved a phenotype continuum between distal involvement and proximal involvement. However, it identified differences in prevalence between the two forms: distal myopathies were predominant in Asia, whereas in Europe and the United States, the proximal forms were most common. The authors concluded that LGMD R2 and Miyoshi myopathy should, for the purposes of clinical treatment, the establishment of future clinical trials and future treatments, be considered to be on the spectrum of a single disease.
