Susceptibility to MH
The great majority of patients susceptible to malignant hyperthermia have no neuromuscular symptoms or signs. They lead full and active lives and indeed there are several examples of MH susceptible individuals who are elite or professional sportsmen or women.
The principal gene implicated in MH susceptibility is RYR1. 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. Other known associations with MH susceptibility are exertional rhabdomyolysis, hyperCKaemia and exertional heat illness.