Author: Henry Rosenberg, MD
With each passing year, it becomes more apparent that mutations in the ryanodine receptor gene (RYR1), the gene most associated with susceptibility of malignant hyperthermia (MH), are also associated with a variety of subclinical as well as overt myopathies. This is true for DNA changes proven to be causal for MH (mutations) as well as variants associated with MH but whose role in the pathophysiology of MH is not firmly established. Several characterized myopathies, such as central core disease, multiminicore disease, and congenital fiber type disproportion, display RYR1 mutations and often predispose to MH susceptibility. Recent studies show that some patients with myalgia and exercise-induced rhabdomyolysis unrelated to known myopathies also harbor RYR1 variants.1 Nevertheless, there are only a few studies of the histologic changes in large cohorts of MH-susceptible patients.2 Such investigations may be scarce because the focus is on the contracture response to halothane, caffeine, and other agents (and more recently on the genetic changes) when patients are referred for MH diagnostic testing, and an expert may not perform or interpret a histologic examination. In addition, earlier studies of MH muscle revealed non-specific changes in muscle histology. Over 30 years ago, Drs. Britt and Kalow first established the MH Investigation Unit at the University of Toronto. Dr. David MacLennan has long been associated with the Unit, and more recently, it has been headed by Dr. Sheila Riazi. It is fortunate that the Investigation Unit has collected and analyzed muscle for histologic changes, performed contracture testing, and implemented molecular genetic analysis when that became available. These data formed the basis for Orlov et al.s3 comprehensive review of the histomorphology of 399 MH-susceptible patients diagnosed by caffeine/ halothane contracture testing during 1992-2011.