Sudden Death in Toddlers Associated with Developmental Abnormalities of the Hippocampus: A Report of Five Cases

Abstract

Sudden unexplained death in childhood (SUDC) is the sudden death of a child older than 1 year of age that remains unexplained after review of the clinical history, circumstances of death, and autopsy with appropriate ancillary testing. We report here 5 cases of SUDC in toddlers that we believe define a new entity associated with hippocampal anomalies at autopsy. All of the toddlers died unexpectedly during the night, apparently during sleep. Within 48 hours before death, 2 toddlers had fever, 3 had a minor upper respiratory tract infection, and 3 experienced minor head trauma. There was a history of febrile seizures in 2 (40%) and a family history of febrile seizures in 2 (40%). Hippocampal findings included external asymmetry and 2 or more microdysgenetic features. The incidence of certain microdysgenetic features was substantially increased in the temporal lobes of these 5 cases compared with the temporal lobes of 39 (control) toddlers with the causes of death established at autopsy (P < 0.01). We propose that these 5 cases define a potential subset of SUDC whose sudden death is caused by an unwitnessed seizure arising during sleep in the anomalous hippocampus and producing cardiopulmonary arrest. Precipitating factors may be fever, infection, and/or minor head trauma. Suggested risk factors are a history of febrile seizures and/or a family history of febrile seizures. Future studies are needed to confirm these initial findings and to define the putative links between sudden death, hippocampal anomalies, and febrile seizures in toddlers.