Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program

Abstract

Background Malignant hyperthermia (MH) susceptibility is a heritable musculoskeletal disorder that can present as a potentially fatal hypermetabolic response to triggering anesthesia agents. Genomic screening for variants in MH-associated genes RYR1 and CACNA1S provides an opportunity to prevent morbidity and mortality. There are limited outcomes data from disclosing variants in RYR1, the most common MH-susceptibility gene, in unselected populations. We sought to identify the rate of MH features or fulminant episodes after triggering agent exposure in an unselected population undergoing genomic screening including actionable RYR1 variants. Methods Geisinger’s MyCode Community Health Initiative is an electronic health record-linked biobank that discloses pathogenic and likely pathogenic variants in clinically actionable genes to patient-participants. Available electronic anesthesia and ambulatory records for participants with actionable RYR1 results returned through December 2020 were evaluated for pertinent findings via double-coded chart reviews and reconciliation. Descriptive statistics for observed phenotypes were calculated. Results One hundred and fifty-two participants had an actionable RYR1 variant disclosed during the study period. None had prior documented genetic testing for MH susceptibility; one had prior contracture testing diagnosing MH susceptibility. Sixty-eight participants (44.7%) had anesthesia records documenting triggering agent exposure during at least one procedure. None received dantrolene treatment or had documented muscle rigidity, myoglobinuria, hyperkalemia, hyperCKemia, severe myalgia, or tea-colored urine. Of 120 possibly MH-related findings (post-operative intensive care unit admissions, hyperthermia, arterial blood gas evaluation, hypercapnia, or tachycardia), 112 (93.3%) were deemed unlikely to be MH events; 8 (6.7%) had insufficient records to determine etiology. Conclusions Results demonstrate a low frequency of classic intra-anesthetic hypermetabolic phenotypes in an unselected population with actionable RYR1 variants. Further research on the actionability of screening for MH susceptibility in unselected populations, including economic impact, predictors of MH episodes, and expanded clinical phenotypes, is necessary.

Treatment and nursing care of a patient diagnosed with malignant hyperthermia after general anesthesia: a case report

“…Malignant hyperthermia (MH) is an infrequent autosomal dominant genetic disorder triggered by volatile anesthetics such as sevoflurane and isoflurane or depolarizing muscle relaxants such as succinylcholine. Prolonged muscular rigidity results in substantial energy expenditure and rapid elevation of body temperature, 1 thereby increasing metabolic activity. Despite its low incidence rate, MH induces rapid disease aggravation and an elevated mortality rate.…”