One Center’s Review of Genetic Testing in Children with Epilepsy Undergoing Presurgical Evaluation
Abstract number :
3.382
Submission category :
12. Genetics / 12A. Human Studies
Year :
2022
Submission ID :
2205136
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:28 AM
Authors :
Kelli Morrissey, MPAS, PA-C – Children's National Hospital; Emily Matuska, BS – Children's National Hospital; Kathryn Havens, PA-C – Children's National Hospital; Nathan Cohen, MD – Children's National Hospital; Tayyba Anwar, MD – Children's National Hospital; Archana Pasupuleti, MD – Children's National Hospital; Tammy Tsuchida, MD – Children's National Hospital; Thuy-Anh Vu, MD – Children's National Hospital; Claudine Sinsioco, MD – Children's National Hospital; Dewi Depositario-Cabacar, MD – Children's National Hospital; Tesfaye Zelleke, MD – Children's National Hospital; William Gaillard, MD – Children's National Hospital; John Schreiber, MD – Children's National Hospital
Rationale: Over the past decade, use of genetic testing in individuals with epilepsy is increasingly employed to establish a diagnosis and guide evaluation and management. Utility of genetic testing is well established in patients with pharmacoresistant developmental and epileptic encephalopathies (DEE). More recently, gene variants have also been identified in focal epilepsies. The use of genetic testing may influence presurgical evaluations and treatment recommendations.
Methods: From an IRB-approved prospective epilepsy surgery database at Children’s National Hospital (including all patients referred for epilepsy surgery), we selected patients with clinical genetic testing. We identified 82 patients and extracted clinical features, type of genetic testing and any positive findings, and type of surgery. Positive findings were defined as pathogenic or likely pathogenic results.
Results: Among the 772 children in the Comprehensive Pediatric Epilepsy Program (CPEP) surgical database, 82 (59% male, 41% female) completed genetic testing. The majority of patients had documented developmental delay (n=59, 72%). Seizure types included focal (50, 61%), multiple types (19, 23%), generalized (18, 22%), and infantile spasms (12, 15%). Abnormal MRI findings were present in 37 (45%) of patients. Intracranial EEG monitoring was done in seven (9%) children and 32 (39%) of children in the cohort went to surgery (Table 1). A genetic diagnosis was established in 13 (16%) children (Table 2). The diagnostic yield was highest for personalized sequencing panel at 40% (2/5). Yields were similar for chromosomal microarray (4/15; 27%), whole exome sequencing (2/8; 25%), and epilepsy gene panel (5/22; 23%). Among the 13 patients with positive genetic findings, one patient with pathogenic DEPDC5 variant had a lesionectomy with Engel Class I outcome now seizure free 7 months, one is scheduled for corpus callosotomy, and five had VNS implantation.
Conclusions: Clinical features, including abnormal development and multiple seizure types, may increase the likelihood of positive genetic findings in children with refractory epilepsy referred for epilepsy surgery. Genetic testing may have implications on the presurgical evaluation and on postsurgical outcomes. Identifying the clinical phenotype can help determine selection of initial genetic testing that will provide the highest yield.
Funding: None
Genetics