Journal article
Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project
Forensic science, medicine, and pathology, Vol.12(1), pp.14-25
03/2016
DOI: 10.1007/s12024-015-9731-3
PMID: 26782962
Abstract
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.
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).
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.
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.
Details
- Title: Subtitle
- Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project
- Creators
- Marco M Hefti - Division of Neuropathology, Department of Pathology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, 10029, USA. marco.hefti@mountsinai.orgJane B Cryan - Department of Pathology, Boston Children's Hospital, Boston, MA, USAElisabeth A Haas - Department of Pathology, Rady Children's Hospital-San Diego, San Diego, CA, USAAmy E Chadwick - Department of Pathology, Rady Children's Hospital-San Diego, San Diego, CA, USALaura A Crandall - SUDC Foundation, Hackensack, NJ, USAFelicia L Trachtenberg - New England Research Institutes, Watertown, MA, USADawna D Armstrong - Department of Pathology, Emeritus, Baylor College of Medicine, Houston, TX, USAMarjorie Grafe - Department of Pathology, Oregon Health and Science University, Portland, OR, USAHenry F Krous - Department of Pediatrics, UCSD School of Medicine, La Jolla, CA, USAHannah C Kinney - Department of Pathology, Boston Children's Hospital, Boston, MA, USA
- Resource Type
- Journal article
- Publication Details
- Forensic science, medicine, and pathology, Vol.12(1), pp.14-25
- Publisher
- United States
- DOI
- 10.1007/s12024-015-9731-3
- PMID
- 26782962
- ISSN
- 1547-769X
- eISSN
- 1556-2891
- Grant note
- name: SUDC Program of the CJ Foundation for SIDS; DOI: 10.13039/100010320, name: Cooper Trewin Memorial SUDC Research Fund; name: Barrett Edward Tallman Memorial Fund; name: Robert’s Program in Sudden Unexpected Death in Pediatrics at Boston Children’s Hospital
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984046934902771
Metrics
47 Record Views