A Proposed North American Approach for Genetic Testing of Individuals at Risk for Malignant Hyperthermia

May 14, 2026

Sheila Riazi, Stacey Watt, Jennifer Plester, & Leslie G. Biesecker

Abstract

Malignant hyperthermia, a pharmacogenetic disorder of skeletal muscle, is a potentially fatal reaction triggered by exposure to volatile anesthetics or succinylcholine. Genetic testing of the three known involved genes (RYR1, CACNA1S, and STAC3) has become the first line of testing for malignant hyperthermia susceptibility. However, genetic testing has sensitivity of only up to 70%. Contracture testing may be used to rule out the disorder for some individuals. This study outlines a stepwise approach, using clinical history and assessment as well as interpretation of genetic variants to balance risks and benefits for individuals at risk of this disorder. This work has received an Affirmation of Value designation from the American Society of Anesthesiologists (Schaumburg, Illinois) and endorsement from the Canadian Anesthesiologists’ Society (Toronto, Canada).

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