Association of ultra‐rare coding variants with genetic generalized epilepsy: A case–control whole exome sequencing study

Abstract

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Utility of Exome Sequencing for Diagnosis in Unexplained Pediatric-Onset Epilepsy

“…We also demonstrate genetic diagnoses in patients with non-DEE epilepsies, for whom there may be lower suspicion of genetic epilepsy and less clinical urgency. While non-DEE epilepsies (eg, GGE, NAGE) are considered influenced by polygenic factors, we found single-gene explanations for some patients and overlap of genes implicated in the DEE and non-DEE groups.…”

“…While there were no overtly unusual features for patients with IGE or self-limited focal epilepsy, it is possible that patients with refractory seizures, who are seen more frequently, had more opportunities to enroll or more questions raised regarding etiology. This may bias our sample toward individuals with identifiable genetic diagnoses, although conversely, our overall yield may have been diminished by inclusion of patients with milder epilepsy phenotypes, such as GGE and NAFE . During the course of this study, we observed variability in genetic testing approval by insurance payers.…”

“…Accordingly, patients, families, and clinicians seek underlying explanations and potentially etiologically specific treatments. Recent studies have demonstrated that a substantial proportion of nonacquired epilepsy is caused by inherited and de novo variants in several brain-expressed genes, providing insight into developmental and epileptic encephalopathies (DEE), genetic generalized epilepsy (GGE), and nonacquired focal epilepsy (NAFE), sometimes involving the same genes …”

Identification of patients with drug‐resistant epilepsy in electronic medical record data using the Observational Medical Outcomes Partnership Common Data Model

“…This research can support rational drug choice in epilepsy care but requires validated definitions in standardized observational data for key outcomes, including drug resistance 11,12 . Second, genetic association studies have the potential to improve understanding of drug resistance and guide treatment and counseling, but also suffer from a shortage of validated phenotypes 13,14 . Third, interdisciplinary guidelines 15 and an American Academy of Neurology quality measure 16 support the referral of patients with DRE to comprehensive epilepsy centers for further management and evaluation for surgical candidacy.…”

“…11,12 Second, genetic association studies have the potential to improve understanding of drug resistance and guide treatment and counseling, but also suffer from a shortage of validated phenotypes. 13,14 Third, interdisciplinary guidelines 15 and an American Academy of Neurology quality measure 16 support the referral of patients with DRE to comprehensive epilepsy centers for further management and evaluation for surgical candidacy. Nonetheless, these centers evaluate fewer than 2% of DRE patients, with >18 years mean disease duration before referral.…”