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Contempo Updates
Clinician's Corner
June 15, 2005

Malignant HyperthermiaUpdate on Susceptibility Testing

Author Affiliations

Contempo Updates Section Editor: Sarah Ringold, MD, Fishbein Fellow.


Author Affiliations: Department of Anesthesiology & Critical Care Medicine, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia (Dr Litman); Department of Medical Education, Saint Barnabas Medical Center, Livingston, New Jersey and Mount Sinai School of Medicine, New York, NY (Dr Rosenberg).

JAMA. 2005;293(23):2918-2924. doi:10.1001/jama.293.23.2918

Quiz Ref IDMalignant hyperthermia (MH) is a pharmacogenetic clinical syndrome that manifests as a hypermetabolic crisis when a susceptible individual is exposed to an anesthetic triggering agent. Clinical signs include unexplained elevation of end-tidal carbon dioxide, muscle rigidity, acidosis, tachycardia, tachypnea, hyperthermia, and evidence of rhabdomyolysis. This process is a result of an abnormally increased release of calcium from the sarcoplasmic reticulum, which is often caused by an inherited mutation in the gene for the ryanodine receptor (RYR1) that resides in the membrane of the sarcoplasmic reticulum. The gold standard for determination of MH susceptibility is the caffeine-halothane contracture test. However, it is invasive, requiring skeletal muscle biopsy and is not widely available. Researchers have begun to map mutations within the ryanodine receptor gene (chromosome 19q13.1) responsible for conferring MH susceptibility. Ryanodine receptor mutations are found in at least 25% of known MH susceptible individuals in North America. Mutation analysis has recently become available in the United States and is expected to play an integral role in the diagnosis of MH susceptibility in the future.