Hippocampal malformation associated with XXXX in early childhood: a neuropathologic study : Part 2 of the investigations of The San Diego SUDC Research Project.

@entity1 @entity410 @entity851 @entity944
PURPOSE: Sudden unexplained death in childhood (SUDC), while rare, accounts for an important fraction of unexpected deaths in @entity1 >1  year of age. Previously we reported an association between @entity410 , hippocampal maldevelopment, and sudden, unexpected deaths in young @entity1 (1-6  years), termed "hippocampal maldevelopment associated with @entity944 (HMASD)." Here, we characterize in greater detail the hippocampal pathology in a large cohort of cases (n  =  42) of this entity, and attempt to define possible new entities responsible for sudden, unexplained death in young @entity1 without HMASD/ @entity410 phenotypes. METHODS: We performed comparative analysis on cases, which we classified in a cohort of 89 sudden and unexpected deaths as HMASD, explained deaths, SUDC with @entity410 phenotype (SUDC-FS) but without hippocampal pathology, and SUDC (without hippocampal pathology or @entity410 phenotype). RESULTS: The frequency of each subgroup was: HMASD 48  % (40/83); SUDC 27  % (22/83); SUDC-FS 18  % (15/83); explained 7  % (6/83). HMASD was characterized clinically by sudden, sleep-related death, term birth, and discovery in the prone position. Key morphologic features of HMASD were focal granule cell bilamination of the dentate gyrus with or without asymmetry and/or malrotation of the hippocampus, associated with significantly increased frequencies of 11 other @entity851 . We identified no other distinct phenotype in the unexplained categories, except for an association of @entity410 without hippocampal maldevelopment. CONCLUSIONS: HMASD is a distinct clinicopathologic entity characterized by a likely developmental failure of neuronal migration in the dentate gyrus. Future research is needed to determine the causal role of HMASD in @entity944 in early childhood.
