Dear Editor,

Malignant Hyperthermia (MH) is a pharmacogenetic syndrome with autosomal dominant inheritance manifested as a crisis of hypermetabolism associated with anesthesia. This syndrome has significant clinical variability, ranging from abortive forms, such as isolated masseter spasm, to fulminant forms. Typical forms are commonly characterized by hypercapnia, tachycardia, muscle rigidity, hyperthermia, metabolic acidosis, and rhabdomyolysis, and can evolve with death in 11−25% of cases. MH is caused by exposure of genetically susceptible individuals to halogenated anesthetic agents and/or depolarizing neuromuscular blocker succinylcholine. The frequency of MH is estimated at 1:50,000 anesthesia in adults and 1:10,000 in children, occurring in all ethnic groups, and more frequently in men than women. Mutations in the Ryanodine Receptor Gene (RYR1) are present in 50% to 70% of families, followed by mutations in the dihydropyridine receptor gene (CACNA1S) in 1% of cases and isolated cases of mutations in the STAC3 gene. To date, the gene locus has not been identified in the remaining MH cases. The clinical diagnosis is based on the history of exposure to triggering agents associated with clinical and laboratory findings, while the definitive diagnosis is based on the In Vitro muscle Contracture Test (IVTC). Alternatively, genetic tests can be used to search for pathogenic variants linked to MH. The main differential diagnoses are Neuroleptic Malignant Syndrome (NMS), Serotonin Syndrome (SS), thyrotoxicosis, sepsis, pheochromocytoma, iatrogenic hyperthermia, ischemic encephalopathy, ascending generalized tonic-clonic seizures following intrathecal use of contrate and overdose of 3,4- Methylenedioxymethamphetamine (MDMA/ecstasy).