Hippocampal formation maldevelopment and sudden unexpected death across the pediatric age spectrum

Sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) are defined as sudden death in a child remaining unexplained despite autopsy and death scene investigation. They are distinguished from each other by age criteria, i.e. with SIDS under 1 year and SUDC over 1 year. Our separate studies of SIDS and SUDC provide evidence of shared hippocampal abnormalities, specifically focal dentate bilamination, a lesion classically associated with temporal lobe epilepsy, across the 2 groups. In this study, we characterized the clinicopathologic features in a retrospective case series of 32 children with sudden death and hippocampal formation (HF) maldevelopment. The greatest frequency of deaths was between 3 weeks and 3 years (81%, 26/32). Dentate anomalies were found across the pediatric age spectrum, supporting a common vulnerability that defies the 1-year age cutoff between SIDS and SUDC. Twelve cases (38%) had seizures, including 7 only with febrile seizures. Subicular anomalies were found in cases over 1 year of age and were associated with increased risk of febrile seizures. Sudden death associated with HF maldevelopment reflects a complex interaction of intrinsic and extrinsic factors that lead to death at different pediatric ages, and may be analogous to sudden unexplained death in epilepsy.