British journal of anaesthesia · 2026
Epidemiology of malignant hyperthermia in the UK from 1988 to 2025: implications for prevalence, mode of inheritance, relative risk associated with RYR1 genotypes, and in vitro contracture test phenotyping.
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Aboelsaod Essameldeen M, Daly Catherine, Fisher Nickla, Hobson Sarah, Garland Huw, Gupta Pawan K, Bilmen Jonathan G, Shepherd Sarah, Robinson Rachel L, Shaw Marie-Anne, Hopkins Philip M
Аннотация
BACKGROUND: We used clinical and genetic data from the UK to analyse the disparity between the incidence of malignant hyperthermia (MH) reactions and the prevalence of variants in the RYR1 gene associated with susceptibility to MH. We examined whether these data are consistent with the clinical risk of MH being inherited as an autosomal dominant trait.
METHODS: The numbers of general anaesthetics delivered in the UK and population data were estimated from national sources. The prevalence of RYR1 variants in the UK population was estimated using UK Biobank data. Bayesian probabilistic modelling calibrated against actual data was used to estimate the prevalence of the clinical risk of MH in the UK (anchored to the incidence of MH reactions from 1988 to 1993) to evaluate the mode of inheritance of the clinical risk of MH and the relative risk associated with different RYR1 variants.
RESULTS: The probability of index cases developing MH with each anaesthetic can be expressed as a constant hazard of 0.46 (95% CI 0.42-0.50, n=375). Our modelling estimated the prevalence of the risk of MH as 1:38 800 (95% credibility interval 1:34 600 to 1:43 700). The incidence of MH has declined over the past 22 yr, but the rate of decline is inconsistent with autosomal dominant inheritance (P<0.33×10-5). The risk of MH varied by up to 125-fold among those with 28 recurrent RYR1 variants.
CONCLUSIONS: These findings support a threshold inheritance model for clinical MH, with implications for diagnostics, both genotyping and in vitro contracture test phenotyping.
METHODS: The numbers of general anaesthetics delivered in the UK and population data were estimated from national sources. The prevalence of RYR1 variants in the UK population was estimated using UK Biobank data. Bayesian probabilistic modelling calibrated against actual data was used to estimate the prevalence of the clinical risk of MH in the UK (anchored to the incidence of MH reactions from 1988 to 1993) to evaluate the mode of inheritance of the clinical risk of MH and the relative risk associated with different RYR1 variants.
RESULTS: The probability of index cases developing MH with each anaesthetic can be expressed as a constant hazard of 0.46 (95% CI 0.42-0.50, n=375). Our modelling estimated the prevalence of the risk of MH as 1:38 800 (95% credibility interval 1:34 600 to 1:43 700). The incidence of MH has declined over the past 22 yr, but the rate of decline is inconsistent with autosomal dominant inheritance (P<0.33×10-5). The risk of MH varied by up to 125-fold among those with 28 recurrent RYR1 variants.
CONCLUSIONS: These findings support a threshold inheritance model for clinical MH, with implications for diagnostics, both genotyping and in vitro contracture test phenotyping.