Date: Tuesday 10th December 2024
Time: 12.30 – 13.30
Title: Incidental RYR1 findings on Whole Genome Sequencing
Speaker: Professor Phil Hopkins, Professor of Anaesthesia, School of Medicine, University of Leeds
Abstract:
Malignant hyperthermia (MH) is a severe, potentially fatal adverse drug reaction in genetically predisposed individuals. It is one of the most common causes of serious morbidity and death in otherwise healthy patients having surgery under general anaesthesia, accounting for 4-10% of all deaths caused by anaesthesia. The reaction is triggered in genetically susceptible individuals by the commonly used, cheap potent inhalation anaesthetic drugs and by succinylcholine. Initially the mortality of MH approached 75% and even since the advent of a potential antidote the mortality is 4-12%. Molecular genetic analysis has contributed to MH diagnostics for 20 years, principally through the identification of variants in the RYR1 gene, but the frequent finding of genotype-phenotype discordance and incomplete understanding of the genetic architecture of MH susceptibility preclude prospective population screening and restrict the use of DNA testing to confirmation of high risk status.
In addition to MH, RYR1 variants are associated with a range of myopathies and was included in the ACMG list of “actionable” genes. I will discuss the laboratory reporting of RYR1 variants with respect to the risk of developing MH under anaesthesia and our experience to date of managing patients in whom RYR1 variants have been found during the course of panel diagnostics and exome/genome sequencing.
Location: St Mary’s Hospital, Manchester M13 9NQ
Cost: Free
Registration: If you would like to attend this lunchtime seminar session, please contact: mrcc@mft.nhs.uk