From PharmGKBMalignant hyperthermia susceptibility (MHS) is a predisposition to a potentially life-threatening, hypermetabolic reaction triggered by potent volatile anesthetics (i.e. desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane) or the depolarizing muscle relaxant succinylcholine. These agents are relatively contraindicated in persons with MHS. MHS is diagnosed either by a positive response to the in vitro contracture test (IVCT) or the caffeine-halothane contracture test (CHCT), or by the presence of a pathogenic variant in RYR1 or CACNA1S that has been identified as causative for MHS (PMID: 30499100). Absence of pathogenetic variants in RYR1 or CACNA1S does not eliminate the chance of MHS based on findings that the genetic cause remains unknown for about half of all MH survivors, with contracture test-confirmed MHS (PMID: 28902675). Both genes are included on the list of actionable secondary findings by the American College of Medical Genetics and Genomics. MHS is inherited in an autosomal dominant manner and a positive result for a patient has familial ramifications. In addition to potential variations in RYR1 or CACNA1S, personal or family history of a reaction to these drugs or agents needs to be considered. Therapeutic guidelines for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
https://www.pharmgkb.org/guidelineAnnotation/PA166180457 From OMIMSusceptibility to malignant hyperthermia (MHS), a skeletal muscle disorder most often inherited as an autosomal dominant trait, is one of the main causes of death due to anesthesia. In susceptible people, a malignant hyperthermia episode is triggered by exposure to commonly used volatile anesthetic agents such as halothane or depolarizing muscle relaxants such as succinyl choline. A fulminant MH crisis is characterized by any combination of hyperthermia, skeletal muscle rigidity, tachycardia or arrhythmia, respiratory and metabolic acidosis, and rhabdomyolysis. Except for this susceptibility to triggering agents, MHS patients are not clinically distinguishable from the general population (summary by Monnier et al., 1997).
Genetic Heterogeneity of Susceptibility to Malignant Hyperthermia
Other MHS loci include MHS2 (154275) on chromosome 17q; MHS3 (154276) on chromosome 7q; MHS4 (600467) on chromosome 3q; MHS5 (601887), caused by mutation in the CACNA1S gene (114208) on chromosome 1q32; and MHS6 (601888) on chromosome 5p.
http://www.omim.org/entry/145600