Last update: 05/06/2006
Background to disease
OMIM #145600 (RYR1 gene OMIM *180901)
Malignant hyperthermia (MH) is a pharmacogenetic disorder which only manifests on exposure to certain inhalational anaesthetics and depolarising muscle relaxants. An MH crisis results in generalised skeletal muscle rigidity especially of the masseter muscle, acidosis, hypoxia and significantly increased body temperature. A crisis can be fatal if not recognised early and treated. Individuals are otherwise phenotypically normal.
Incidence of MH in the population has been estimated to be 1/2000.
MH is genetically heterogeneous but the majority (70%) of UK families show linkage to the ryanodine receptor gene (RYR1) on chromosome 19q12.1-13.2 which encodes the skeletal muscle Ca2+ release channel. To date more than 100 RYR1 mutations have been identified in association with MH and/or central core disease (CCD), the majority missense. Thus genetic diagnosis has been introduced cautiously according to guidelines established by the European MH Group (www.emhg.org), in conjunction with the established in vitro contracture test (IVCT) carried out on muscle biopsy specimens. Genetic testing is only offered to families where MH has been confirmed by a positive IVCT in at least one family member. Up to 23 missense mutations, where in vitro functional analysis of recombinant RYR channels has indicated an alteration in normal function may be screened for. Genetic testing is appropriate for approximately 50% UK families at present.
MH may also be associated with Central Core Disease (see separate page).
Laboratory Analysis
Contact scientist: Rachel Robinson
New referrals should initially be directed to Prof PM Hopkins or Dr PJ Halsall at the MH Investigation Unit at St James’ University Hospital (0113 206 5274).
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Test |
Target reporting time (working days) |
|
| 1. |
ARMS/RFLP analysis for: 1. Family members with a known mutation 2. Index case screening for UK recurrent mutations (11)
|
20 |
| 2. |
ARMS/RFLP analysis for: 1. Additional mutations (UK prevalent) 2. Additional mutations (not UK prevalent)
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20 |
|
Screening for novel mutations by cDNA analysis and sequencing |
Under development | |
|
Linkage analysis |
20 |