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Science 8 May 1992:
Vol. 256. no. 5058, pp. 789 - 794
DOI: 10.1126/science.256.5058.789
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Articles

Science, Vol 256, Issue 5058, 789-794
Copyright © 1992 by American Association for the Advancement of Science

articles

Malignant hyperthermia

DH MacLennan and MS Phillips

Banting & Best Department of Medical Research, University of Toronto, Ontario, Canada.

In humans genetically predisposed to malignant hyperthermia, anesthesia can induce skeletal muscle rigidity, hypermetabolism, and high fever, which, if not immediately reversed, can lead to tissue damage or death. The corresponding condition in swine leads to stress-induced deaths and devalued meat products. Abnormalities in the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) have been implicated in the cause of both the porcine and human syndromes by physiological and biochemical studies and genetic linkage analysis. In swine, a single founder mutation in the ryanodine receptor gene (RYR1) can account for all cases of malignant hyperthermia in all breeds, but a series of different RYR1 mutations are likely to be uncovered in human families with MH. Moreover, lack of linkage between malignant hyperthermia and RYR1 in some families indicates a heterogeneous genetic basis for the human syndrome.


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