Information for Geneticists
Information for Geneticists and Genetic Counsellors about Malignant Hyperthermia (MH)
MH is a potentially life-threatening condition which is avoidable if anaesthesia is given with no triggering agents.
Some MH susceptible individuals present outside of the operating theatre. Known associations with MH susceptibility are exertional rhabdomyolysis, hyperCKaemia, exertional heat illness, central core disease and multiminicore myopathy. There are also rare reports of MH susceptible individuals who present with episodes of fever and muscle rigidity unrelated to drug exposure that can prove fatal.
Inheritance of MH can be best explained by a threshold model: many MH families appear to have more than one genetic factor making a major contribution to the risk of MH susceptibility.
MHANZ member laboratories (all of whom follow the EMHG testing guidelines) offer an in-vitro contracture test (IVCT) to family members who test negative for the family mutation.
MHANZ is conservative with interpreting predictive genetic tests. MHANZ recognises many families that have discordance between genotype and phenotype suggesting the presence of a second mutation or a modifying variant. Absence of the family mutation is not an adequate test for non-susceptibility.
As a result genetic diagnosis of MH with the presence of a known causative mutation is possible but the converse is not true.
For patient safety, individuals carrying a potentially a potentially MH causative RYR1 variant should be regarded at increased risk for MH until further diagnostic tests, i.e., an IVCT, have been performed.
Many RYR1 variants have been found in MH and non-MH susceptible individuals. The EMHG has developed a scoring matrix for pathogenicity prediction http://www.emhg.org/genetics
Ideally, genetic testing for MH should be done in consultation with an MH Diagnostic Unit.
