Malignant hyperthermia
At a minimum, these SNPs are known to be related, and others may also be
Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder in which potent inhaled anesthetics and the muscle relaxant suxamethonium disrupt skeletal muscle calcium homeostasis. It is a major cause of anesthetic related deaths in otherwise fit individuals. Exhibiting an autosomal dominant mode of inheritance, the incidence of MH has been estimated as high as 1:2,000. The true figure is difficult to know as the majority of susceptible individuals are completely asymptomatic until exposed to triggering drugs, and only 2% of the population will receive these drugs in any given year. Furthermore, the development of the clinically detectable features of hypermetabolism typical of MH depend on the anesthetic dose and duration.[PMID 16917943]
In the US, the Malignant Hyperthermia Association of the United States (MHAUS) provides information about this disorder, including ways to test for it.
The primary form of MH, MHS1, is caused by heterozygous mutations in the RYR1 gene, inherited in a dominant fashion. The complete list of 31 causative RYR1 mutations leading to MHS1 according to the European MH Group can be found on the RYR1 page.
While there are many mutations scattered over this large gene, many of them are actually "private", meaning they are so rare that they have only been seen once (i.e. in one family). Some variations have been seen in multiple families, typically differing between ethnicities. Examples of recurring mutations in certain countries include:
- United Kingdom
- rs121918593 (perhaps accounting for 40% of UK MHS1 cases)
- rs118192177 (perhaps 10%)
- rs121918592 (perhaps 8%)
- Germany
- Switzerland
- France
