BACKGROUND
Ryanodine receptor type 1 (RYR1) sequence variants are pathogenic for malignant hyperthermia. Variant carriers have a subtle increase in resting myoplasmic calcium concentration compared with nonaffected individuals, but whether this has metabolic effects in daily life is unknown.
OBJECTIVES
We analysed the potential effect of malignant hyperthermia-pathogenic RYR1 sequence variants on BMI as a single factor. Due to the heterogeneity of genetic variants predisposing to malignant hyperthermia, and to incomplete information about their regional distribution, we describe the prevalence of RYR1 variants in our population.
DESIGN
A retrospective cohort study.
SETTING
A single University hospital.
PATIENTS
Patients from malignant hyperthermia families with pathogenic RYR1 sequence variants were selected if BMI was available.
OUTCOME MEASURES
BMI values were compared amongst malignant hyperthermia susceptible (MHS) and malignant hyperthermia-negative individuals using hierarchical multivariable analyses adjusted for age and sex and considering family clustering. Variant prevalence was calculated.
RESULTS
The study included 281 individuals from 42 unrelated malignant hyperthermia families, 109 of whom were MHS and carriers of the familial RYR1 sequence variants. Median [IQR] BMI in MHS individuals with pathogenic RYR1 variants was 22.5 kg m−2 [21.3 to 25.6 kg m−2]. In malignant hyperthermia-negative individuals without variants, median BMI was 23.4 kg m−2 [21.0 to 26.3 kg m−2]. Using multivariable regression adjusted for age and sex, the mean difference was −0.73 (95% CI −1.51 to 0.05). No carrier of a pathogenic RYR1 sequence variant was found to have BMI higher than 30 kg m−2. Only 10 RYR1 variants from the list of the European MH Group were found in our cohort, the most common being p.Val2168Met (39% of families), p.Arg2336His (24%) and p.Arg614Cys (12%).
CONCLUSION
The observed tendency towards lower BMI values in carriers of malignant hyperthermia-pathogenic RYR1 sequence variants points to a possible protective effect on obesity. This study confirms regional differences of the prevalence of malignant hyperthermia-pathogenic RYR1 sequence variants, with just three variants covering 75% of Swiss MHS families.
TRIAL REGISTRATION
This manuscript is based on a retrospective analysis.
