Clinical and genetic epidemiology of malignant hyperthermia

Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disorder that occurs in susceptible patients in exposure to triggering volatile anaesthetics and/or succinylcholine. With the advances in the anaesthetic practice in recent years, we have to re-think about our understanding of the clinical epidemiology of MH. The development in the anaesthetic agents and techniques would influence the clinical presentation of MH and alter the outcomes of the disease. On the other hand, the emergency nature of the anaesthetic MH reaction undermines the quality of clinical information available for retrospective studies about the condition.
Genetically, the introduction of next-generation sequencing (NGS) methods enabled screening of the whole ryanodine receptor 1 gene (RYR1). As more than 300 variants have been detected in the RYR1, and of these, 48 variants have been functionally characterised as causative for MH, we have to evaluate the effects of these mutations on the clinical presentation of MH. A genotype-phenotype correlation should enable us to better understand the variable penetrance of MH. Additionally, we will be able to evaluate the relationship between MH and other RYR1-related muscle diseases; namely, congenital myopathies. The overlap between different subtypes of congenital myopathies and the potential risk of MH in these different subtypes originating from this overlap is an ongoing scientific perplexity.
Finally, we will try to gather information about the extent of the MH problem in Egypt, a country with a population approaching 100 million and many inadequacies in the operating health systems.