RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction.
Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a common cause of exertional rhabdomyolysis, accounting for up to 30% of rhabdomyolysis episodes in otherwise healthy individuals. Common triggers are exercise and heat and, less frequently, viral infections, alcohol and drugs. Most subjects are normally strong and have no personal or family history of malignant hyperthermia. Heat intolerance and cold-induced muscle stiffness may be a feature. Recognition of this (probably not uncommon) rhabdomyolysis cause is vital for effective counselling, to identify potentially malignant hyperthermia-susceptible individuals and to adapt training regimes. Studies in various animal models provide insights regarding possible pathophysiological mechanisms and offer therapeutic perspectives.
Department of Neurology, Radboud University Medical Centre, R. Postlaan 4 (route 935), P.O. Box 9101, 6500 Nijmegen (935), The Netherlands. Electronic address: nicol.voermans@radboudumc.nl.
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Voermans
Department of Anaesthesia, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
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Snoeck
Department of Paediatric Neurology, Neuromuscular Service, Evelina Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, London, UK; Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section, London, UK; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
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Jungbluth
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001642:Bicycling; D002648:Child; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D063806:Myalgia / Q000209:etiology; D005082:Physical Exertion; D012206:Rhabdomyolysis / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D055815:Young Adult
D019837:Ryanodine Receptor Calcium Release Channel
Exercise; Exertional rhabdomyolysis; Genetic; Myopathy; Rhabdomyolysis; Ryanodine receptor (RyR1); Skeletal muscle ryanodine receptor (RYR1) gene