Susceptibility to MH
MH susceptibility predisposes to a potentially fatal reaction to the most commonly used anaesthetic drugs. Susceptible individuals are usually healthy but exposure to the triggering drugs causes a loss of calcium regulation in skeletal muscle cells leading to muscle spasm, a profound increase in metabolic activity and muscle cell disruption. Survival depends on prompt recognition of the evolving reaction and appropriate treatment by the anaesthetist. If a patient is known to be at increased risk for MH, a reaction can be avoided by the use of alternative anaesthetic drugs that are known not to trigger the condition.
While most patients susceptible to MH are apparently healthy unless exposed to the triggering anaesthetics, there are some MH susceptible individuals who present in other ways. Known associations with MH susceptibility are exertional rhabdomyolysis, hyperCKaemia and exertional heat illness. Patients with congenital myopathies with a RYR1 aetiology (central core disease, multiminicore myopathy) are also at risk of developing malignant hyperthermia if their RYR1 mutation results in gain of function of the RyR1 channel. Loss of function RYR1 mutations are not associated with MH susceptibility. There are also rare reports of MH susceptible children with non-specific clinical and histological myopathic features who present with apparently spontaneous episodes of fever and muscle rigidity that can prove fatal. Late onset RYR1 myopathy may also be associated with MH susceptibility.
Mode of inheritance
MH susceptibility was originally described as an autosomal dominant condition with incomplete penetrance. There is mounting evidence that MH susceptibility is one of a growing number of presumed single gene disorders that deviates from a simple Mendelian model of inheritance. Indeed, inheritance of MH can be best explained by a threshold model: approximately 8% of UK MH families appear to have more than one genetic factor making a major contribution to the risk of MH susceptibility.