Malignant hyperthermia (MH) is a potentially lethal disorder triggered in susceptible individuals
on exposure to common anaesthetic agents. Crises reflect the consequences of disturbed skeletal
muscle calcium homeostasis. MH is an autosomal dominant, genetically heterogeneous trait. Defects
in a single major gene have been assumed to determine susceptibility status in individual families.
However, in some pedigrees phenotypic and genotypic data are discordant. One explanation, in
contrast to the current genetic model, is that susceptibility is dependent upon the effects of more
than one gene. Using the transmission disequilibrium test we assessed the involvement of 8 MH
candidate loci (RYR1, CACNA1S, CACNA2D1, MHS4 at 3q13.1, MHS6 at 5p, LIPE, DM1,
dystrophin) by analysis of data from 130 MH nuclear families. Results suggested that variations in
more than one gene may influence MH susceptibility in single families.