Since recognition of MH as an inherited condition in 1960 at least six potential genetic loci have been proposed. MH-associated mutations have been found in two genes so far: the RYR1 gene (MIM 180 901) and the CACNA1S gene (MIM 114 208). Products of these genes play key roles in the process of excitation-contraction (EC) coupling and in maintenance of Ca2+ homeostasis in skeletal muscle cells. MH genetic research has shown that RYR1 is the major causal gene for MH as well as for an associated congenital myopathy, central core disease (CCD).

Genetic testing, based on advances in MH genetic research, is playing an increasingly important role in MH diagnostics. It proved especially useful in early diagnosis of children and patients who cannot undergo the caffeine-halothane contracture test (CHCT). Nevertheless, genetic testing for MH has low sensitivity as there are a limited number of well-characterized mutations currently accepted as being MH causative by the European Malignant Hyperthermia Group. Development of a more comprehensive genetic test depends on establishment of an exhaustive collection of MH-causative mutations. Thus, the search for new mutations in diverse populations as well as validation of their MH causality continues.

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