Dysferlinopathies with late onset (beyond the age of 30) have phenotypic peculiarities

Dysferlinopathies cover several clinical entities having as a common substratum a deficiency in dysferlin, a protein involved in the repair mechanisms of the membrane of the muscle fiber. Reduced initially to a Miyoshi-type distal myopathy, the phenotypic spectrum quickly extended to pure proximal forms (such as girdle muscular dystrophy or LGMD) and especially to combined proximo-distal forms. Inherited in the autosomal recessive mode, dysferlinopathies are currently the subject of a natural history study called JAIN COS for therapeutic trials. 

In an article published in March 2021, clinicians from the Institute of Myology collected clinical and biological data from patients with late-onset dysferlinopathy who participated in the international natural history protocol, the criterion for the onset being set at 30 years. Forty-eight patients met the selection criteria, with the median age at first symptom being 37 years and the majority phenotype being LGMD. Compared to the group with earlier onset of the disease, the authors note a higher frequency of atypical phenotypes, a lower CPK average rate, less progression (loss of walking occurring later after the onset of symptoms), and more frequent atypias on muscle biopsy. 


Deep phenotyping of an international series of patients with late onset dysferlinopathy. Fernández-Eulate G, Querin G, Moore U, Behin A, Masingue M, Bassez G, Leonard-Louis S, Laforêt P, Maisonobe T, Merle PE, Spinazzi M, Solé G, Kuntzer T, Bedat-Millet AL, Salort-Campana E, Attarian S, Péréon Y, Feasson L, Graveleau J, Nadaj-Pakleza A, Leturcq F, Gorokhova S, Krahn M, Eymard B, Straub V; Jain COS Consortium, Evangelista T, Stojkovic T. Eur J Neurol. 2021 Mar 13. doi: 10.1111/ene.14821. Online ahead of print.