Genomic biomarkers of SUDEP in brain and heart.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but how to predict which patients are at risk and how to prevent it remain uncertain. The underlying pathomechanisms of SUDEP are still largely unknown, but the general consensus is that seizures somehow disrupt normal cardiac or respiratory physiology leading to death. However, the proportion of SUDEP cases exhibiting cardiac or respiratory dysfunction as a critical factor in the terminal cascade of events remains unresolved. Although many general risk factors for SUDEP have been identified, the development of reliable patient-specific biomarkers for SUDEP is needed to provide more accurate risk prediction and personalized patient management strategies. Studies in animal models and patient groups have revealed at least nine different brain-heart genes that may contribute to a genetic susceptibility for SUDEP, making them potentially useful as genomic biomarkers. This review summarizes data on the relationship between these neurocardiac genes and SUDEP, discussing their brain-heart expression patterns and genotype-phenotype correlations in mouse models and people with epilepsy. These neurocardiac genes represent good first candidates for evaluation as genomic biomarkers of SUDEP in future studies. The development of validated reliable genomic biomarkers for SUDEP has the potential to transform the clinical treatment of epilepsy by pinpointing patients at risk of SUDEP and allowing optimized, genotype-guided therapeutic and prevention strategies.