MYH7-related myopathies: clinical, myopathological and genotypic spectrum in a multicentre French cohort

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 96; no. 5; pp. 453 - 461
• Main Authors: Bahout, Marie, Severa, Gianmarco, Kamoun, Emna, Bouhour, Françoise, Pegat, Antoine, Toutain, Annick, Lagrange, Emmeline, Duval, Fanny, Tard, Celine, De la Cruz, Elisa, Féasson, Léonard, Jacquin-Piques, Agnès, Richard, Pascale, Métay, Corinne, Cavalli, Michele, Romero, Norma Beatriz, Evangelista, Teresinha, Sole, Guilhem, Carlier, Robert Yves, Laforêt, Pascal, Acket, Blandine, Behin, Anthony, Fernández-Eulate, Gorka, Léonard-Louis, Sarah, Quijano-Roy, Susana, Pereon, Yann, Salort-Campana, Emmanuelle, Nadaj-Pakleza, Aleksandra, Masingue, Marion, Malfatti, Edoardo, Stojkovic, Tanya, Villar-Quiles, Rocío Nur
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.05.2025; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aged; Asymptomatic; Biopsy; Cardiac Myosins - genetics; Cardiomyopathy; Child; Cohort Studies; Family medical history; Female; Foot diseases; France; Genetic testing; GENETICS; Genotype; Genotype & phenotype; Humans; Kinases; Magnetic Resonance Imaging; Male; Microscopy; Middle Aged; MRI; Muscle, Skeletal - diagnostic imaging; Muscle, Skeletal - pathology; Muscular Diseases - diagnostic imaging; Muscular Diseases - genetics; Muscular Diseases - pathology; Musculoskeletal system; Mutation; MYOPATHY; Myosin Heavy Chains - genetics; Neck; Neuromuscular; NEUROPATHOLOGY; Phenotype; Retrospective Studies; Scoliosis; Young Adult; France; MYOPATHY; NEUROPATHOLOGY; GENETICS; MRI
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2024-334263

BackgroundMyosin heavy chain 7 (MYH7)-related myopathies (MYH7-RMs) are a group of muscle disorders linked to pathogenic variants in the MYH7 gene, encoding the slow/beta-cardiac myosin heavy chain, which is highly expressed in skeletal muscle and heart. The phenotype is heterogeneous including distal, predominantly axial or scapuloperoneal myopathies with variable cardiac involvement.MethodsWe retrospectively analysed the clinical, muscle MRI, genetic and myopathological features of 57 MYH7 patients. Patients received a thorough neurological (n=57, 100%), cardiac (n=51, 89%) and respiratory (n=45, 79%) assessment. Muscle imaging findings and muscle biopsies were reappraised in 19 (33%) and 27 (47%) patients, respectively.ResultsWe identified three phenotypes with varying degrees of overlap: distal myopathy (70%), scapuloperoneal (23%) and axial with peculiar cervical spine rigidity called the ‘sphinx’ phenotype (7%). 14% of patients had either dilated cardiomyopathy, hypertrophic cardiomyopathy or left ventricular non-compaction cardiomyopathy. 31% of patients had prominent respiratory involvement, including all patients with the ‘sphinx’ phenotype. Muscle MRI showed involvement of tibialis anterior, followed by quadriceps, and erector spinae in patients with axial phenotype. Cores represented the most common myopathological lesion. We report 26 pathogenic variants of MYH7 gene, 9 of which are novel.Conclusions MYH7-RMs have a large phenotypic spectrum, including distal, scapuloperoneal or axial weakness, and variable cardiac and respiratory involvement. Tibialis anterior is constantly and precociously affected both clinically and on muscle imaging. Cores represent the most common myopathological lesion. Our detailed description of MYH7-RMs should improve their recognition and management.