Background: Malignant hyperthermia (MH) is a rare but serious pharmacogenetic disorder triggered by specific anesthetic agents, leading to a rapid and often fatal hypermetabolic response. While its genetic roots – primarily involving RYR1 and CACNA1S mutations – are well documented, many susceptible individuals remain undiagnosed until they are exposed to the triggering anesthetic. Despite dantrolene being an instrumental drug in combatting MH mortality, global access remains inconsistent, and morbidity rates remains high. Current diagnostic tools are invasive and limited to specialized centers, and routine screening is rarely feasible. Summary: This review explores how recent advances in multi-omics – genomics, proteomics, metabolomics, transcriptomics, and radiomics – are reshaping our understanding of MH pathophysiology. From chronic calcium dysregulation and mitochondrial dysfunction to shifts in energy metabolism and subtle muscle changes, a complex picture is emerging. Integrative analyses reveal promising biomarkers for early detection, while CRISPRbased gene editing and machine learning offer potential pathways for future targeted interventions. Noninvasive imaging, blood-based metabolic profiling, and genomic risk prediction may soon offer safer, more effective screening tools for anesthesia planning. Key Messages: Ultimately, a shift from reactive crisis management to proactive risk identification could redefine how we approach MH – potentially improving patient outcomes and saving lives.
Thachuk et al. (Thu,) studied this question.