Molecular genetic detection of susceptibility to malignant hyperthermia in Belgian families

Malignant hyperthermia is an autosomal dominant myopathy triggered by volatile anesthetics or succinylcholine in susceptible persons. While in vitro contracture testing (IVCT) is the gold standard to establish malignant hyperthermia (MH) susceptibility, genetic analysis is increasingly used to diagnose this condition. This work aimed to determine the frequency and distribution of ryanodine receptor (RYR1) mutations in the Belgian MH-population as investigated by IVCT in our centre, as well as the discordance rates between the 2 techniques. Sequence analysis of 16 RYRI-exons in 29 selected families resulted in the detection of 10 mutations (4 Gly341Arg, 2 Arg614Leu, and 1 Cys35Arg, Arg614Cys, Arg2163Cys and Arg2435His). Discordance between IVCT and mutation analysis was observed in only 6 out of 96 individuals from 4 different families. No mutation-positive/ IVCT-negative diagnosis was found. Genetic evaluation of RYR1-mutations can secure a diagnosis and aid in genetic counselling of individual family members but only in those families in which significant clinical information is present, as well as phenotyping by IVCT has been realized.