@article{a5b0fc02045f400c9f365ef89780e51b,
title = "Confirmation of cause of death via comprehensive autopsy and whole exome molecular sequencing in people with epilepsy and sudden unexpected death",
abstract = "BACKGROUND: Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. METHODS AND RESULTS: Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non-SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2. CONCLUSIONS: This study examined one of the largest single-center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A; postmortem whole exome sequencing identified 18 ultrarare variants.",
keywords = "Cardiomyopathies, Channelopathies, Genetics, Sudden death",
author = "Chahal, {C. Anwar A.} and Tester, {David J.} and Fayyaz, {Ahmed U.} and Keerthi Jaliparthy and Khan, {Nadeem A.} and Dongmei Lu and Mariha Khan and Aradhana Sahoo and Aiswarya Rajendran and Knight, {Jennifer A.} and Simpson, {Michael A.} and Behr, {Elijah R.} and So, {Elson L.} and {St. Louis}, {Erik K.} and Reichard, {R. Ross} and Edwards, {William D.} and Ackerman, {Michael J.} and Somersv, {Virend K.}",
note = "Funding Information: This work was supported by the and National Center for Research Resources the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number 1 UL1 TR002377 RR024150-01. Chahal and Somers are supported by National Institutes of Health HL65176 and HL134885. Chahal is supported by the American Heart Association (Award number 17POST33400211). Ackerman and Tester are supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. The authors acknowledge support from the Mayo Foundation for Medical Education and Research, Department of Medicine Team Science Award. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. Funding Information: No off-label medication use. St. Louis reports that he receives research support from the Mayo Clinic Center for Translational Science Activities, supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number 1 UL1 RR024150-01. Publisher Copyright: {\textcopyright} 2021 The Authors and Mayo Clinic. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. JAHA is available at: www.ahajournals.org/journal/jaha.",
year = "2021",
month = dec,
day = "7",
doi = "10.1161/JAHA.121.021170",
language = "English",
volume = "10",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "American Heart Association, Inc.",
number = "23",
}