Abstracts

Rationale:
Epilepsy surgery outcomes are wide-ranging and have an enormous impact on patient quality of life. Case series have suggested that patients with a genetic etiology (other than mTOR pathway abnormalities) may have less favorable outcomes than their peers.1-2 Herein we report on 3 patients having previously undergone epilepsy surgery and subsequently found to have a genetic etiology of their epilepsy.
Method:
A retrospective chart review was performed of all patients having undergone resective epilepsy surgery at The Children’s Hospital of Colorado between 2009-2019. Factors previously described in the literature as having potential impact on epilepsy surgery outcomes were recorded, as well as any genetic testing previously performed. Results192 patients were identified that had undergone resective epilepsy surgery. Of these, 43 had genetic testing performed, and 12 had positive results. Of the 12 patients with positive results, 5 were related to TS, NF1, or familial cavernous malformations. 4 patients had benign variants, and 3 had genetic findings thought to be pathogenic and causative of their epilepsy.  All 3 of these patients had developmental delay, 2 prior to onset of seizures, and 1 of 3 had multifocal epileptiform discharges on EEG. All 3 were determined to be surgical candidates and underwent sEEG followed by resective surgery. All 3 had a recurrence of seizures, Engel class 4b. Patient 1 was found to have a heterozygous mutation in the WDR45 gene, a variant which has been observed in several individuals affected with Beta-propeller protein-associated neurodegeneration (BPAN). Subsequent brain MRI demonstrated symmetric susceptibility in the globi pallidi and substantia nigra consistent with BPAN. Patient 2 had an epilepsy panel which demonstrated a pathologic CHD2 variant (de novo).  A paternally inherited variant in DEPDC5, but which has variable penetrance, is thought to also contribute.  Patient 3 had a pathogenic, de novo GABRA2 mutation identified on whole exome sequencing.
Conclusion:
Patients who have refractory focal epilepsy and a work-up indicative of adequate candidacy for resective epilepsy surgery, may still have unfavorable outcomes, including seizure recurrence. Previously identified factors that help predict surgical outcomes have been enormously beneficial to epilepsy surgery patients, and identification of further factors is imperative. All 3 of the patients described herein eventually had genetic testing; demonstrating a genetic etiology of their epilepsy, which may have impacted the pre-surgical planning. Further study is warranted to determine the impact genetic testing can have on the pre-surgical work up and planning for surgical outcomes for epilepsy surgery candidates. References: •Koelman, B., Maurits, W.S., Braun, K. Genetic testing for epilepsy surgery. Epileptologie 2018; 35:21-28 •Skjei, K., Church, E., Harding, B., Santi, M., Holland-Bouley, K., Clancy, R., Porter., B, Heuer, G., Marsh, E. Clinical and histopathological outcomes in patient with SCN1A mutations undergoing surgery for epilepsy. J Neurosurg Pediatr 2015; 16:668-674.
Funding:
:None