Seizures and Sudden Death Beyond SUDEP.

ABSTRACT

Many physicians and researchers are familiar with the tragic phenomenon known as sudden infant death syndrome (SIDS), the leading cause of postneonatal mortality in high-resource countries. A less familiar category of unexplained deaths is the problem of sudden unexplained death in childhood (SUDC), a more rare and unusual presentation of sudden death in children who are no longer infants and whose reasons for death defy explanation. A substantial body of research in SUDC now supports the possibility of an overlap with epilepsy and associated sudden death in that context (SUDEP). Stemming from the first contemporary reports of SUDC, we have learned that a disproportionate number of these children have personal and/or family histories of febrile seizures,1 in many cases, inherited in an autosomal dominant manner.2 Their febrile seizures can be associated with abnormalities in their temporal lobes,3,4 including bilamination of the dentate gyrus and other findings conventionally associated with temporal lobe epilepsy, implicating potential epilepsy-related mechanisms.5 Further evaluation of this emerging epilepsy-related phenotype has led to the identification of genetic variants in SCN1A and other epilepsy-associated genes,6,7 moving SUDC away from being considered an unexplained phenomenon to one where the working hypothesis includes a role for genetic predisposition and epilepsy-like mechanisms in the deaths, even without an established history of epilepsy. Nonetheless, because the terminal events of these seemingly healthy children are unexpected and unobserved, the clinical manifestations of whatever underlying vulnerabilities exist-generally discovered posthumously-remain a matter of speculation.