Date of Award
Thesis - Open Access
Sudden Unexpected Death in Epilepsy [SUDEP] is one of the major causes of death within the world population that has epilepsy (Partemi, et al., 2014). There is no clear consensus on the underlying mechanism and are theorized to be heterogeneous in nature (Nashef et al., 2012). Some of these mechanisms are cardiac arrhythmias, and dysfunctions in either the respiratory or brainstem arousal systems (Ruthirago et al., 2018). Postmortem testing could provide further understanding of SUDEP and could be used as an asset to medical examiners. In this study we seek to evaluate the utility of postmortem genetic testing as part of a pilot study utilizing in-house postmortem molecular analysis at NYC-OCME on SUDEP cases retrospectively and prospectively. Thirty-two cases were analyzed by In-house Cardiac & Epilepsy Sudden Death Molecular Analysis. Among the 19 definite or definite SUDEP plus cases, two likely pathogenic variants have been identified in two definite SUDEP cases. Testing yield, percentage of cases with positive results is calculated to be 10.5%. 17 of the 19 definite or definite SUDEP cases (89.5%, one case has both a likely pathogenic variant and a variant of uncertain significance [VUS] identified) have one or more VUS identified. One case (5.3%) has a negative result with no variants identified in the 257 genes tested. A likely pathogenic splice-site missense variant was found in SCN2A in a 9 year-old female with White/Caucasian ethnicity. A likely pathogenic frameshift variant was found in CACNA1H in a 27 year-old male with Hispanic ethnicity. Our results show the utility of postmortem molecular testing in SUDEP. Accurate variant interpretation and classification as well as risk assessment is essential for patients and families affected by SUDEP. More research and data collection on variants discovered through NGS in varied racial/ethnic populations is required.
An, Yu and Villarreal, Alejandra M. Cantú, "Post Mortem Genetic Testing in Sudden Unexpected Death in Epilepsy [SUDEP]: A Pilot Story" (2020). Human Genetics Theses. 85.