Multiple interacting gene products may influence susceptibility to malignant hyperthermia

Malignant hyperthermia (MH) is a potentially lethal disorder triggered in s usceptible individuals on exposure to common anaesthetic agents. Crises ref lect the consequences of disturbed skeletal muscle calcium homeostasis. MH is an autosomal dominant, genetically heterogeneous trait. Defects in a sin gle major gene have been assumed to determine susceptibility status in indi vidual families. However, in some pedigrees phenotypic and genotypic data a re discordant. One explanation, in contrast to the current genetic model, i s 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, LI PE, DM1, dystrophin) by analysis of data from 130 MH nuclear families. Resu lts suggested that variations in more than one gene may influence MH suscep tibility in single families.