Information for Geneticists and Genetic Counsellors
Ideally, genetic testing for MH should be done in consultation with an MH Diagnostic Unit to provide the most comprehensive risk assessment for the individual.
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Inheritance of MH can be best explained by a threshold model: many MH families appear to have more than one genetic factor making a contribution to the risk of MH susceptibility.
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The EMHG maintains a list of known causative mutations for MH which includes variants in RYR1 and CACNA1S.
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Pathogenic and likely pathogenic mutations are reported in RYR1 for myopathy as well as MH. Not all pathogenic mutations for myopathy confer MH risk.
MHANZ member laboratories (all of whom follow the EMHG testing guidelines) offer an in-vitro contracture test (IVCT) to members of families with a history of MH who test negative for the family mutation.
In a family where an MH episode has occurred, testing negative for the causative mutation is not sufficient for that family member's risk to revert to the population risk. There are other as yet unknown factors which increase the risk of MH. The rate of positive IVCT in some of these families approaches 30% (RMH MHDU audit 2025)
