Malignant hyperthermia (MH) is a rare clinical syndrome characterized by hypermetabolism and triggered by specific
anesthetic agents. The mechanism of this abnormal reaction is due to uncontrolled
calcium flux in the skeletal muscles resulting in a variable clinical syndrome of
muscle rigidity, respiratory and
metabolic acidosis, and elevation of temperature. The specific genetic defect underlying this condition has not been identified in humans, though in susceptible swine a mutation of the gene for the
ryanodine receptor, a large
protein which comprises the
calcium channel in the sarcoplasmic reticulum, has been identified recently. Inheritance in humans appears to be autosomal dominant with variable penetrance. Patients with MH rarely have physical or laboratory signs of muscle disease. However, scattered case reports and investigations of individuals with known
myopathies and other muscle related problems, such as acute
rhabdomyolysis or idiopathic persistently elevated
creatine kinase, suggest a possible association of MH with a variety of
neuromuscular diseases and stress syndromes. This association is very strong in the case of
central core disease (CCD) where it is supported by clinical and laboratory evidence, including the proximity of the CCD gene to the
ryanodine receptor gene on chromosome 19. A variety of other diseases have been implicated and can be classified as possibly associated (
King-Denborough syndrome,
Duchenne muscular dystrophy) or unlikely to be associated (
myotonia congenita,
sudden infant death syndrome, limb girdle dystrophy,
neuroleptic malignant syndrome, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)