TY - JOUR
T1 - Hippocampal malformation associated with sudden death in early childhood
T2 - a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project
AU - Hefti, Marco M.
AU - Cryan, Jane B.
AU - Haas, Elisabeth A.
AU - Chadwick, Amy E.
AU - Crandall, Laura A.
AU - Trachtenberg, Felicia L.
AU - Armstrong, Dawna D.
AU - Grafe, Marjorie
AU - Krous, Henry F.
AU - Kinney, Hannah C.
N1 - Funding Information:
We thank the many families for their willingness to participate in this study. We also thank the coroners, medical examiners, and pathologists who helped in ensuring the evaluation of the forensic autopsy materials. We appreciate the administrative assistance of Ms. Kelley Journey, MPH, in study closure. We thank Drs. Richard D. Goldstein and Joseph J. Volpe for thoughtful reading of the manuscript in preparation. This study was supported by grants from the SUDC Program of the CJ Foundation for SIDS, Cooper Trewin Memorial SUDC Research Fund, Barrett Edward Tallman Memorial Fund, and Robert’s Program in Sudden Unexpected Death in Pediatrics at Boston Children’s Hospital.
Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Purpose: Sudden unexplained death in childhood (SUDC), while rare, accounts for an important fraction of unexpected deaths in children >1 year of age. Previously we reported an association between febrile seizures, hippocampal maldevelopment, and sudden, unexpected deaths in young children (1–6 years), termed “hippocampal maldevelopment associated with sudden death (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 children without HMASD/febrile seizure 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 febrile seizure phenotype (SUDC-FS) but without hippocampal pathology, and SUDC (without hippocampal pathology or febrile seizure 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 developmental abnormalities. We identified no other distinct phenotype in the unexplained categories, except for an association of febrile seizures 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 sudden death in early childhood.
AB - Purpose: Sudden unexplained death in childhood (SUDC), while rare, accounts for an important fraction of unexpected deaths in children >1 year of age. Previously we reported an association between febrile seizures, hippocampal maldevelopment, and sudden, unexpected deaths in young children (1–6 years), termed “hippocampal maldevelopment associated with sudden death (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 children without HMASD/febrile seizure 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 febrile seizure phenotype (SUDC-FS) but without hippocampal pathology, and SUDC (without hippocampal pathology or febrile seizure 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 developmental abnormalities. We identified no other distinct phenotype in the unexplained categories, except for an association of febrile seizures 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 sudden death in early childhood.
KW - Dentate gyrus
KW - Febrile seizures
KW - Neurogenesis
KW - Sudden unexplained death in childhood (SUDC)
KW - Sudden unexplained death in epilepsy (SUDEP)
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U2 - 10.1007/s12024-015-9731-3
DO - 10.1007/s12024-015-9731-3
M3 - Article
C2 - 26782962
AN - SCOPUS:84958047068
VL - 12
SP - 14
EP - 25
JO - Forensic Science, Medicine, and Pathology
JF - Forensic Science, Medicine, and Pathology
SN - 1547-769X
IS - 1
ER -