Genetic testing for susceptibility to Malignant Hyperthermia is already offered by a number of commercial laboratories (see the MHAUS web site for details). A new laboratory, the Robert Guthrie Biochemical and Molecular Genetics Laboratory at Buffalo General Medical Center, Buffalo, New York is now offering genetic testing for MH and related disorders. Dr. Georgirene Vladutiu, Director of the Guthrie laboratory, has informed MHAUS that the laboratory now offers targeted sequencing of two of the genes known to be associated with MH, the RYR1(ryanodine receptor type 1 gene) and CACNA1S (voltage-dependent L type alpha 1S ) gene. Causative variants for MH have been reported in the RYR1 gene in up to 70% of MH susceptibles and in the CACNA1S gene in 1% of cases.
The laboratory test will detect all 37 functionally characterized pathogenic (MH causative ) DNA variants in these genes. (These variants are listed on the European Malignant Hyperthermia Group’s website at www.emhg.org.) In addition the test will also detect another 99 DNA variants that, although not completely characterized, are predicted by various biologic tools to be disease causing (pathogenic).
According to Dr. Vladutiu, candidates for the genetic test include (a) those confirmed to be MH susceptible by the caffeine-halothane muscle biopsy contracture test or by a confirmed clinical episode of MH as determined by an MH expert. (b) family members of an individual in whom a known mutation that is causative for MH has been found, (c) patients with muscle breakdown associated with heat and/or exertion(also known as rhabdomyolysis), heat stroke, statin-induced myopathy (i.e., those on cholesterol lowering drugs who experience severe muscle pain or weakness), (d) unexplained, persistent elevation in blood of the muscle enzyme creatine kinase, and (e) unexplained marked temperature elevation and other signs of MH associated with muscle breakdown in association with other drugs.
Because MH is dominantly inherited, only one copy of a pathogenic, causal DNA variant is required for susceptibility to MH. Importantly, the absence of a known causative mutation does not rule out MH susceptibility since the identification of all genes or DNA variants that can cause MH is incomplete. Molecular genetic testing, which only requires a blood sample, may obviate the need for the muscle biopsy diagnostic test particularly in individuals where a DNA variant that is associated with MH susceptibility has been found in another family member. We caution that decision to undergo genetic testing should be made in conjunction with a physician or genetic counselor who can not only assess the indication for the genetic test, but can interpret the results of the test.
For more detailed information, see the Full Test List or Test Profiles & Gene Sequence Analysis at www.rgbmgl.org. A Mutation Analysis for Metabolic Myopathy form signed by an ordering physician and a DNA Testing Consent Form (“Online Forms”) signed by the individual to be tested are also required.
Additional contact information is as follows:
Robert Guthrie Biochemical & Molecular Genetics Laboratory
Kaleida Health Laboratories
Buffalo General Medical Center
Room A-762, 100 High Street
Buffalo, NY 14203
Kaleida Health Laboratories is a College of American Pathology accredited diagnostic laboratory certified by the New York State Department of Health and the Pennsylvania Department of Health.