Continued progress in understanding the molecular genetics of malignant hyperthermia

摘要: A little over 50 years ago, Denborough and Lovell described the syndrome known today as malignant hyperthermia (MH). Little was about this disorder at time other than it carried a high fatality rate characterized by explosive in an otherwise apparently healthy individual undergoing general anesthesia. The unravelling of principal features involved combination astute clinical observations, fortuitous association with similar pigs, assiduous laboratory investigations involving contributions from many countries. Seminal to understanding MH were made individuals associated University Toronto, particularly Drs. Beverly Britt, Werner Kalow, Roderick Gordon, David MacLennan, their coworkers. In issue Journal, Dr. MacLennan et al. continue expand on earlier work MH, molecular genetics allied myopathy, Central Core Disease. Although inheritance pattern humans 1980s, turning point story occurred 1990 when MacLennan’s team identified mutation ryanodine receptor gene causal for swine model MH. However, has proven be far more complex obscure. This is due, part, inherent complexity syndrome; variety presentations that may mimicked several situations; lack typical phenotypic signs absence anesthesia; genes; potentially, scores DNA variants lead pathophysiologic abnormality namely, calcium dysregulation skeletal muscle cell. Since become manifest without warning progress rapidly life-threatening hypercarbia, breakdown, acidosis, hyperthermia, much effort been expended attempting identify those risk syndrome. mainstay diagnostic test biopsy contracture first Britt Kalow early 1970s. entails exposure biopsied calcium-releasing agents, such halothane, caffeine, ryanodine, /or chloro-m-cresol. time, served clarify Disease, multiple Clearly, not applicable either screening or rapid identification susceptibility. Furthermore, most tests, sensitivity specificity are 100%. Nevertheless, standard against which tests judged. One main current goals research related development minimally invasive, highly accurate Molecular holds promise meeting goal. fact, genetic testing susceptibility already available countries present but requires careful patient selection because limited testing. road goal line sensitive specific replete obstacles, just inherited disorders. For instance, although (RYR-1) release channel sarcoplasmic reticulum often syndrome, regulatory proteins, dihydropyridine and, recently, calsequestrin, intracellular H. Rosenberg, MD (&) Department Medical Education Clinical Research, Saint Barnabas Center, Livingston, NJ, USA e-mail: hrosenberg@sbhcs.com