Miyoshi myopathy and limb girdle muscular dystrophy R2 are the same disease

• DOI: 10.1016/j.nmd.2021.01.009
• Publication Date: 2021-01-22T03:32:53Z
• Authors: Ursula Moore; Heather Gordish; Jordi Diaz-Manera; Meredith K. James; Anna G. Mayhew; Michela Guglieri; Roberto Fernandez...; Laura E. Rufibach; Jia Feng; Andrew M. Blamire; Pierre G. Carlier; Simone Spuler; John W. Day; Kristi J. Jones; Diana X. Bharucha...; Emmanuelle Salort...; Alan Pestronk; Maggie C. Walter; Carmen Paradas; Tanya Stojkovic; Madoka Mori-Yoshi...; Elena Bravver; Elena Pegoraro; Linda Pax Lowes; Jerry R. Mendell; Kate Bushby; Volker Straub
• Keywords: Adult; Male; 0301 basic medicine; [54] Cohort study; Adolescent; [SDV]Life Sciences [q-bio]; Clinical trials methodology; [16] Clinical neurology examination; Young Adult; 03 medical and health sciences; Humans; [185] Muscle disease; Clinical neurology examination; [176] All neuromuscular disease; Child; Muscle disease; Muscle Weakness; [21] Clinical trials methodology; Infant, Newborn; Infant; Middle Aged; Magnetic Resonance Imaging; 3. Good health; [SDV] Life Sciences [q-bio]; Distal Myopathies; Muscular Atrophy; [16] Clinical neurology examination; [176] All neuromuscular disease; [185] Muscle disease; [21] Clinical trials methodology; [54] Cohort study; Phenotype; Muscular Dystrophies, Limb-Girdle; Child, Preschool; Disease Progression; Integrative Biomedicine [Topic 3]; Female; Function and Dysfunction of the Nervous System; Cohort study; All neuromuscular disease

This study aims to determine clinically relevant phenotypic differences between the two most common phenotypic classifications in dysferlinopathy, limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MMD1). LGMDR2 and MMD1 are reported to involve different muscles, with LGMDR2 showing predominant limb girdle weakness and MMD1 showing predominant distal lower limb weakness. We used heatmaps, regression analysis and principle component analysis of functional and Magnetic Resonance Imaging data to perform a cross-sectional review of the pattern of muscle involvement in 168 patients from the Jain Foundation's international Clinical Outcomes Study for Dysferlinopathy. We demonstrated that there is no clinically relevant difference in proximal vs distal involvement between diagnosis. There is a continuum of distal involvement at any given degree of proximal involvement and patients do not fall into discrete distally or proximally affected groups. There appeared to be geographical preference for a particular diagnosis, with MMD1 being more common in Japan and LGMDR2 in Europe and the USA. We conclude that the dysferlinopathies do not form two distinct phenotypic groups and therefore should not be split into separate cohorts of LGMDR2 and MM for the purposes of clinical management, enrolment in clinical trials or access to subsequent treatments.