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In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed.<\/jats:p>","DOI":"10.1136\/bmjsem-2016-000151","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T22:48:33Z","timestamp":1473288513000},"page":"e000151","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?"],"prefix":"10.1136","volume":"2","author":[{"given":"Renata S","family":"Scalco","sequence":"first","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Snoeck","sequence":"additional","affiliation":[{"name":"MH-investigation Unit, Department of Anesthesia, Canisius-Wilhelmina Hospital, Nijmegen, 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