Ryanodine receptor gene point mutation and malignant hyperthermia susceptibility

Malignant hyperthermia (MH) is a rare clinical syndrome, triggered in susceptible subjects by a variety of anaesthetic agents and muscle relaxants, and is the commonest cause of death due to general anaesthesia. Previous studies have reported that inherited mutations in the ryanodine receptor (RYR1) gene co-segregated, in some families, with MH susceptibility; lack of linkage between MH and the RYR1 gene in some other families indicates a heterogenous genetic basis for the syndrome. The in vitro contracture test (IVCT) on muscle biopsy specimens is considered to be the most reliable test for establishing the diagnosis of MH. With the identification of RYR1 point mutations this might in turn result in non-invasive methods for the presymptomatic diagnosis of MH. In the present study we investigated four families suspected to be at risk of MH susceptibility; in all subjects histopathological examination and IVCT were performed on muscle biopsy specimens. We undertook a mutation analysis of RYR1 gene testing for the presence of five point mutations; in one pedigree a C1840 --> T point mutation was detected, strictly segregating with in vitro MI-I susceptibility.