Education  |   January 2018
Malignant Hyperthermia Susceptibility and Related Diseases
Author Notes
  • From the Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania (R.S.L., S.M.G.); Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (J.J.D.); and Department of Anesthesia and Pain Management, University Health Network, University of Toronto, Toronto, Ontario, Canada (S.R.).
  • Corresponding articles on pages 8 and 168.
    Corresponding articles on pages 8 and 168.×
  • Figure 1 was enhanced by Sara Jarret, C.M.I.
    Figure 1 was enhanced by Sara Jarret, C.M.I.×
  • Submitted for publication October 2, 2016. Accepted for publication April 7, 2017.
    Submitted for publication October 2, 2016. Accepted for publication April 7, 2017.×
  • Address correspondence to Dr. Litman: Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19104. Litmanr@email.chop.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Education / Clinical Concepts and Commentary / Patient Safety / Pediatric Anesthesia
Education   |   January 2018
Malignant Hyperthermia Susceptibility and Related Diseases
Anesthesiology 1 2018, Vol.128, 159-167. doi:10.1097/ALN.0000000000001877
Anesthesiology 1 2018, Vol.128, 159-167. doi:10.1097/ALN.0000000000001877
MALIGNANT hyperthermia (MH) is an inherited disorder of skeletal muscle that manifests clinically as a hypermetabolic crisis when a susceptible individual receives a halogenated inhalational anesthetic agent or succinylcholine.1–3  The clinical signs that ensue from this exposure in susceptible individuals include hypercapnia, masseter muscle and/or generalized muscle rigidity, acidosis, peaked T waves that indicate hyperkalemia, and hyperthermia and are caused by the dysregulated entry of myoplasmic calcium, which results in a hypermetabolic cascade involving sustained muscular contractures, depletion of adenosine triphosphate, and muscle cell death.4  The inheritance of pathogenic variants (i.e., mutations) in three genes are primarily associated with MH susceptibility and account for the genetic basis of approximately 70% of patients investigated (fig. 1). The majority of MH–associated variants are found within the RYR1 gene that encodes the skeletal muscle ryanodine receptor type I protein.2,5–7  This protein regulates the movement of calcium from the sarcoplasmic reticulum into the intracellular space of the muscle cell. In MH–susceptible individuals, abnormalities of the ryanodine receptor result in the accumulation of excessive myoplasmic calcium in the presence of one of the anesthetic triggering agents. Nearly 700 variants have been identified in RYR1; however, only 35 have been functionally validated as MH–causative pathogenic variants (an up-to-date list as well as the criteria for causality may be found at the European Malignant Hyperthermia Group website).8  The remainder await validation studies.
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