Malignant hyperthermia (malignant hyperthermia) - Genes CACNA1S and RYR1.  

Malignant hyperthermia is a serious reaction to certain drugs that are frequently used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, and a muscle relaxant used to temporarily paralyze a person during a surgical procedure. If they are given these drugs, people at risk of malignant hyperthermia may experience muscle stiffness, breakdown of muscle fibers, high fever, acidosis and tachycardia. Without prompt treatment, complications of malignant hyperthermia can be life threatening. Affected people may not know they have altered unless undergo tests or have a severe reaction to anesthesia during a surgical procedure. While this condition often occurs in people with no other serious medical problems, certain hereditary muscular disorders, are associated with susceptibility to malignant hyperthermia.

They have been described at least six forms of susceptibility to malignant hyperthermia, which are caused by mutations in different genes. Mutations in genes CACNA1S, located on the long (q) arm of chromosome 1 at position 32 (1q32) and RYR1, located on the long (q) arm of chromosome 19 at position 13.1 (19q13.1) increase the risk of developing malignant hyperthermia.

The CACNA1S and RYR1 genes encode proteins that play essential roles in skeletal muscles. For the body to move normally, skeletal muscles must contract and relax in a coordinated manner. Muscle contractions are caused by the flow of ions in muscle cells. Proteins synthesized in the coding CACNA1S and RYR1 genes are involved in the movement of calcium ions inside muscle cells. Mutations in these genes cause large amounts of calcium ions are released into the muscle cells. Excess available calcium ions causes skeletal muscles to contract abnormally, leading to muscle stiffness. An increase in the concentration of calcium ions inside muscle cells also leads to an increase in body temperature and acidosis.

Mutations in the RYR1 gene are responsible for a form of the condition known as MHS1. These mutations account for most cases of malignant hyperthermia. Mutations in the gene CACNA1S constitute a very small percentage of cases of malignant hyperthermia. Have identified two mutations in the gene CACNA1S are associated with an increased risk for this disorder. One of these mutations the amino acid arginine replaced by the amino acid cysteine at position 1086 of the protein (Arg1086Cys). The other mutation replaces the amino acid arginine for the amino acid histidine in the same position protein (Arg1086His). Another way of altering, MHS5, results from mutations in the gene CACNA1S. These mutations are less frequent, causing less than one percent of all cases of malignant hyperthermia susceptibility.

Susceptibility to malignant hyperthermia is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to increase the risk of a serious reaction to certain drugs used during surgery. In most cases, an affected person inherits the altered gene from a parent who is also at risk of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with malignant hyperthermia, by complete PCR amplification of the exons of the genes and RYR1 CACNA1S respectively and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).