{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:44:09Z","timestamp":1794267849312,"version":"4.9.0"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Rhabdomyolysis is a potentially life-threatening condition characterized by acute skeletal muscle breakdown. In addition to well-described external triggers, a genetic contribution is increasingly recognized. We aimed to (I) review the genetic diagnostic approach of rhabdomyolysis, (II) evaluate the clinical characteristics indicative of a genetic susceptibility with the \u2018RHABDO\u2019 acronym, and (III) assess the predictive value of the presence RHABDO features for identifying genetic variants. Methods: In this retrospective two-center study, 122 patients underwent genetic testing for rhabdomyolysis since the introduction of whole exome sequencing (WES) in 2013. The presence of RHABDO features was compared between those with (likely) pathogenic variants and those with benign or no identified variants or variants of uncertain significance. Results: The testing methods included panel-based WES (82%), Sanger sequencing (49%), and full WES (24%), of which 52 patients (43%) underwent multiple methods. A (likely) pathogenic variant was identified in 13 patients (11%), in all of whom \u22652 RHABDO features were present. The positive predictive value for \u22652 features was 14%, while the negative predictive value was 100%. Conclusions: These results highlight the relevance of WES in further elucidating the genetic basis of rhabdomyolysis and demonstrated that RHABDO is a valuable tool for selecting patients who should undergo genetic testing.<\/jats:p>","DOI":"10.3390\/genes16090995","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:26:31Z","timestamp":1756189591000},"page":"995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rhabdomyolysis in the Era of Next-Generation Sequencing: Selecting Patients with a High Likelihood of a Genetic Susceptibility Using \u2018RHABDO\u2019 Features"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-6772","authenticated-orcid":false,"given":"Nick","family":"Kruijt","sequence":"first","affiliation":[{"name":"Department of Neurology, Radboudumc Research Institute for Medical Innovation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 XZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4028-1113","authenticated-orcid":false,"given":"Sanne A. J. H.","family":"van de Camp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboudumc Research Institute for Medical Innovation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 XZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-9024","authenticated-orcid":false,"given":"Jasper J.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboudumc Research Institute for Medical Innovation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 XZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7735-3267","authenticated-orcid":false,"given":"Luuk R.","family":"van den Bersselaar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboudumc Research Institute for Medical Innovation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 XZ Nijmegen, The Netherlands"},{"name":"Malignant Hyperthermia Investigation Unit, Department of Anesthesiology, Canisius Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands"},{"name":"Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meyke","family":"Schouten","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thatjana","family":"Gardeitchik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-3427","authenticated-orcid":false,"given":"Heinz","family":"Jungbluth","sequence":"additional","affiliation":[{"name":"Muscle Signalling Section, Randall Centre for Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine (FoLSM), King\u2019s College London, London SE1 1UL, UK"},{"name":"Department of Paediatric Neurology, Neuromuscular Service, Evelina London Children\u2019s Hospital, Guy\u2019s and St Thomas\u2019 Hospital NHS Foundation Trust, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4702-9380","authenticated-orcid":false,"given":"Salman","family":"Bhai","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Neuromuscular Center, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas, TX 75231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke J.","family":"van der Kooi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam University Medical Center, Amsterdam Neuroscience Institute, University of Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik-Jan","family":"Kamsteeg","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol C.","family":"Voermans","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboudumc Research Institute for Medical Innovation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 XZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ejim.2006.09.020","article-title":"The syndrome of rhabdomyolysis: Pathophysiology and diagnosis","volume":"18","author":"Giannoglou","year":"2007","journal-title":"Eur. 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