title: Neuromuscular conditions associated with malignant hyperthermia in paediatric patients: A 25-year retrospective study.
abstract: Malignant Hyperthermia (MH) is a rare pharmacogenetic syndrome that can be fatal and the risk of MH in non RYR1-related disorders is unknown. We conducted a retrospective study to determine the prevalence of neuromuscular disorders among patients with MH at our centre. Patients who were admitted to the Hospital for Sick Children during the study period of January 1, 1990 to April 1, 2015 with a CK level > 8000 IU/L, or who received dantrolene, or who had a clinical diagnosis of MH were included. Medical records of 166 patients who met the inclusion criteria were reviewed and 13 patients were identified with MH-like reactions. Nine patients were classified as having true MH after review of the anaesthesia record and genetic testing results were available for 7 patients, 5 of whom had mutations in RYR1. Of the four patients who had severe reactions to anaesthesia but did not meet the criteria for true MH, two had Duchenne muscular dystrophy (DMD). In this retrospective study over 25 years, RYR1 mutations were the most common cause of MH in our cohort, and of these, one third had an underlying neuromuscular diagnosis. Genetic testing of RYR1 is indicated for all patients with MH, and anaesthetic precautions should be considered for any child with symptoms of neuromuscular disease.
authors.affiliation: Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: Bamaga
authors.affiliation: Malignant Hyperthermia Investigation Unit, Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Riazi
authors.affiliation: Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Amburgey
authors.affiliation: Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shaun
authors.initials: S
authors.lastname: Ong
authors.affiliation: Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Halliday
authors.affiliation: Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Phedias
authors.initials: P
authors.lastname: Diamandis
authors.affiliation: Departments of Critical Care Medicine and Paediatrics, Neuroscience and Mental Health Program, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Guerguerian
authors.affiliation: Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: James J
authors.initials: JJ
authors.lastname: Dowling
authors.affiliation: Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: grace.yoon@utoronto.ca.
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
mesh_terms: D000293:Adolescent; D000758:Anesthesia / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003620:Dantrolene / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008305:Malignant Hyperthermia / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation; D009468:Neuromuscular Diseases / Q000150:complications / Q000453:epidemiology*; D012189:Retrospective Studies; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D003620:Dantrolene
keywords: Duchenne Muscular Dystrophy (DMD); Malignant Hyperthermia (MH); RYR1