Genetics of MH
All of our physical characteristics are determined by our genes. Each gene carries a code that is used to make a unique protein. We each have two copies of every gene, one inherited from our mother and the other from our father. The only exception to this is the genes that are present on our sex chromosomes. As far as we know, the genetic defects responsible for malignant hyperthermia are not located on the sex chromosomes.
When a fault or change occurs in a gene, the effect of the change will depend on the nature of the gene change and the protein encoded by the gene. In many instances a gene change in one out of the two copies of the gene will not have any noticeable effect. Some genetic disorders, however, require only one of the two copies to be affected by a gene change for the genetic disorder to be apparent. Such a genetic disorder is called a dominant condition because the one gene change affects the function of the protein encoded by the gene.
In most MH families, MH susceptibility appears to be inherited in a dominant fashion. However, in at least 10% of MH families the inheritance of MH susceptibility can only be explained by the presence of more than one gene change. This could be a result of more than one gene change in a single gene or gene changes in more than one gene. This situation is by no means unique to MH, with several other apparently simple genetic disorders being influenced by changes in more than one gene.
To date, the most commonly implicated gene associated with MH is called the RYR1 gene. This gene encodes a protein that is only made in skeletal muscle tissue where it has a major role in controlling the calcium release within the muscle cell. Many gene changes in the RYR1 gene have been found but only a minority of these have been shown to cause an MH response. Indeed, there are several gene changes in the RYR1 gene that have been found in people who are not susceptible to MH. Two other genes have been implicated in MH susceptibility but their involvement is rare, affecting less than 1% of MH cases. In approximately 30% of MH cases RYR1 and the two other known genes have been excluded as the cause of MH susceptibility.