ArticleAnesthesiology2019
An Assessment of Penetrance and Clinical Expression of Malignant Hyperthermia in Individuals Carrying Diagnostic Ryanodine Receptor 1 Gene Mutations.
Article in Anesthesiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- JSA guideline for management of malignant hyperthermia in 2025.Journal of anesthesia · 2026Guideline
- Considerations for diverse RYR1 variants in malignant hyperthermia susceptible patients: a report of two cases.BMC anesthesiology · 2026Article
- Monogenic Syndromes as a Cause of Adverse Drug Reactions in the Russian Population.International journal of molecular sciences · 2026Article
- A proposed North American approach for genetic testing of individuals at risk for malignant hyperthermia.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2026Review
- Postoperative malignant hyperthermia in a one-year-old girl with down syndrome: a case report.Journal of anesthesia · 2026Article
- A Proposed North American Approach for Genetic Testing of Individuals at Risk for Malignant Hyperthermia.Anesthesiology · 2026Article
- Malignant Hyperthermia in Slavonic cohort - clinical and genetic findings beyond standard diagnostics.Orphanet journal of rare diseases · 2026Article
- Clinical and Genetic Spectrum ofMolecular syndromology · 2026Article
- Assessing Allele Frequency Information: A Study of Variant Curation Expert Panel Guidelines.Human mutation · 2026Article
- A Rare Case of Suspected Malignant Hyperthermia in a Three-Day-Old Neonate: A Case Report.Cureus · 2026Article
- Genetic Testing for Malignant Hyperthermia Susceptibility-Threading the Needle in the Haystack.Genes · 2025Review
- Anabolic androgenic steroids and illicit drugs as potential modulating factors in malignant hyperthermia: a case series.Anaesthesiology intensive therapy · 2025Article
- Updating probability of pathogenicity for RYR1 and CACNA1S exon variants in individuals without malignant hyperthermia after exposure to triggering anesthetics.Pharmacogenetics and genomics · 2025Article
- Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.American journal of human genetics · 2024Article
- Current Practices in Pharmacogenomics.Pediatric clinics of North America · 2023Review
- Rebounds of sevoflurane concentration during simulated trigger-free pediatric and adult anesthesia.BMC anesthesiology · 2023Article
- Malignant Hyperthermia in PICU-From Diagnosis to Treatment in the Light of Up-to-Date Knowledge.Children (Basel, Switzerland) · 2022Review
- Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ryanodine receptor 1 (RYR1) mutations in two patients with tubular aggregate myopathy.The European journal of neuroscience · 2022Article
- Comment on "Overlapping Mechanisms of Exertional Heat Stroke and Malignant Hyperthermia: Evidence vs. Conjecture".Sports medicine (Auckland, N.Z.) · 2022Article
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Authors and funding
9 authors at 1 institution in 4 countries.
Funding
Abstract
backgroundMalignant hyperthermia (MH) is a potentially lethal disorder triggered by certain anesthetics. Mutations in the ryanodine receptor 1 (RYR1) gene account for about half of MH cases. Discordance between the low incidence of MH and a high prevalence of mutations has been attributed to incomplete penetrance, which has not been quantified yet. The authors aimed to examine penetrance of MH-diagnostic RYR1 mutations and the likelihood of mutation carriers to develop MH, and to identify factors affecting severity of MH clinical expression.
methodsIn this multicenter case-control study, data from 125 MH pedigrees between 1994 and 2017 were collected from four European registries and one Canadian registry. Probands (survivors of MH reaction) and their relatives with at least one exposure to anesthetic triggers, carrying one diagnostic RYR1 mutation, were included. Penetrance (percentage of probands among all genotype-positive) and the probability of a mutation carrier to develop MH were obtained. MH onset time and Clinical Grading Scale score were used to assess MH reaction severity.
resultsThe overall penetrance of nine RYR1 diagnostic mutations was 40.6% (93 of 229), without statistical differences among mutations. Likelihood to develop MH on exposure to triggers was 0.25 among all RYR1 mutation carriers, and 0.76 in probands (95% CI of the difference 0.41 to 0.59). Penetrance in males was significantly higher than in females (50% [62 of 124] vs. 29.7% [30 of 101]; P = 0.002). Males had increased odds of developing MH (odds ratio, 2.37; 95% CI, 1.36 to 4.12) despite similar levels of exposure to trigger anesthetics. Proband's median age was 12 yr (interquartile range 6 to 32.5).
conclusionsNine MH-diagnostic RYR1 mutations have sex-dependent incomplete penetrance, whereas MH clinical expression is influenced by patient's age and the type of anesthetic. Our quantitative evaluation of MH penetrance reinforces the notion that a previous uneventful anesthetic does not preclude the possibility of developing MH.
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