British journal of anaesthesia
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Case Reports
A multi-dimensional analysis of genotype-phenotype discordance in malignant hyperthermia susceptibility.
Malignant hyperthermia (MH) susceptibility is an inherited condition, diagnosed either by the presence of a pathogenic genetic variant or by in vitro caffeine-halothane contracture testing. Through a multi-dimensional approach, we describe the implications of discordance between genetic and in vitro test results in a patient with a family history of possible MH. ⋯ Available data do not confirm or exclude an increased risk of MH for this patient. Further research is needed to correlate RyR1 functional assays, including the current gold standard testing for MH susceptibility, with clinical phenotypes. The pathogenicity of genetic variants associated with MH susceptibility should be re-evaluated.
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Existing genetic information can be leveraged to identify patients with susceptibilities to conditions that might impact their perioperative care, but clinicians generally have limited exposure and are not trained to contextualise this information. We identified patients with genetic susceptibilities to anaesthetic complications using a perioperative biorepository and characterised the concordance with existing diagnoses. ⋯ We identified patients with genetic susceptibility to perioperative complications using an open source script designed for clinician use. We validated this application in a retrospective analysis for three conditions with well-characterised inheritance, and showed that not all genetic susceptibilities were documented in the EHR.