Systematic Review of the Genetics of Sudden Unexpected Death in Epilepsy: Potential Overlap With Sudden Cardiac Death and Arrhythmia‐Related Genes

Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the gen...

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Published in:Journal of the American Heart Association Vol. 9; no. 1; p. e012264
Main Authors: Chahal, C. Anwar A., Salloum, Mohammad N., Alahdab, Fares, Gottwald, Joseph A., Tester, David J., Anwer, Lucman A., So, Elson L., Murad, Mohammad Hassan, St Louis, Erik K., Ackerman, Michael J., Somers, Virend K.
Format: Journal Article
Language:English
Published: England John Wiley and Sons Inc 07.01.2020
Wiley
Subjects:
Adolescent
Adult
Arrhythmias, Cardiac - diagnosis
Arrhythmias, Cardiac - genetics
Arrhythmias, Cardiac - mortality
channelopathy
Child
Child, Preschool
Death, Sudden, Cardiac - etiology
epilepsy
Epilepsy - diagnosis
Epilepsy - genetics
Epilepsy - mortality
Female
Genetic Predisposition to Disease
Genetic Variation
Humans
Infant
K‐channel
long QT syndrome
Male
Middle Aged
Phenotype
Potassium Channels - genetics
Risk Assessment
Risk Factors
seizure
sodium channels
Sodium Channels - genetics
Sudden Unexpected Death in Epilepsy - etiology
Systematic Review and Meta‐analysis
Young Adult
epilepsy
sudden death
seizure
long QT syndrome
sodium channels
channelopathy
K‐channel
ISSN:2047-9980, 2047-9980
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Summary:Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP. Methods and Results PubMed, MEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus were searched through April 4, 2017. English language human studies analyzing SUDEP for known sudden death, ion channel and arrhythmia-related pathogenic variants, novel variant discovery, and copy number variant analyses were included. Aggregate descriptive statistics were generated; data were insufficient for meta-analysis. A total of 8 studies with 161 unique individuals were included; mean was age 29.0 (±SD 14.2) years; 61% males; ECG data were reported in 7.5% of cases; 50.7% were found prone and 58% of deaths were nocturnal. Cause included all types of epilepsy. Antemortem diagnosis of Dravet syndrome and autism (with duplication of chromosome 15) was associated with 11% and 9% of cases. The most frequently detected known pathogenic variants at postmortem were in Na and K ion channel subunits, as were novel potentially pathogenic variants (11%). Overall, the majority of variants were of unknown significance. Analysis of copy number variant was insignificant. Conclusions SUDEP case adjudication and evaluation remains limited largely because of crucial missing data such as ECGs. The most frequent pathogenic/likely pathogenic variants identified by molecular autopsy are in ion channel or arrhythmia-related genes, with an ≈11% discovery rate. Comprehensive postmortem examination should include examination of the heart and brain by specialized pathologists and blood storage.
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ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.119.012264