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.