Malignant Hyperthermia—Molecular Testing

Malignant hyperthermia (MH) is triggered by all inhalative anesthetics as well as depolarizing muscle relaxants in genetically predisposed individuals. Presymptomatic testing is important in this potentially fatal pharmacogenetic disease. In vitro challenging of muscle samples with halothane and caffeine is the basis of contracture testing, which until recently was the only accepted diagnostic procedure. Contracture testing is invasive and needs an open skeletal muscle biopsy. Therefore, research in MH focuses on the development of less invasive procedures. In approximately 85% of MH families, segregation analyses with microsatellite markers showed positive linkage of the MH susceptible (MHS) phenotype to the genetic locus of the skeletal muscle endoplasmatic calcium channel (ryanodine receptor, RYR1). Guidelines for molecular genetic diagnosis of MH were recently published and allow for molecular genetic diagnosis of MH susceptibility in case of identification of a MH causative mutation. Because of the locus and allelic heterogeneity of MH, absence of MH associated mutations do not allow for negative MH diagnosis.