Epilepsy surgery outcomes in patients with GATOR1 gene complex variants: Report of new cases and review of literature. (April 2023)

• Record Type: Journal Article
• Authors: Sahly, Ahmed N; Whitney, Robyn; Costain, Gregory; Chau, Vann; Otsubo, Hiroshi; Ochi, Ayako; Donner, Elizabeth J; Cunningham, Jessie; Jones, Kevin C; Widjaja, Elysa; Ibrahim, George M; Jain, Puneet
• Is Part Of: Seizure. Volume 107(2023)
• Page Start: 13
• Page End: 20
• Publication Date: 2023-04
• Subjects: GATOR1, mTORopathy, FCD -- BOSD -- Sleep-related hypermotor epilepsy -- SEEG; ASMs Anti-seizure medications -- BOSD Bottom-of-sulcus dysplasia -- DEPDC5 DEP domain containing protein 5 -- DRE Drug-resistant Epilepsy -- ES Epileptic Spasms -- FCD Focal cortical dysplasia -- FIAS Focal impaired awareness seizures -- FNMOS Focal non-motor onset seizures -- GATOR1 GAP activity towards rags complex 1 -- GDD Global developmental delay -- MEG Magnetoencephalography -- MRgLITT MR-guided laser interstitial thermal therapy -- mTOR mammalian target of rapamycin -- NPRL2 Nitrogen permease regulator-like 2 -- NPRL3 Nitrogen permease regulator-like 3 -- PET Positron Emission Tomography; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2023.03.004
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: Pathogenic GATOR1 variants - important etiology of medically refractory epilepsy in children. GATOR1-related disease spectrum wide – includes focal seizures, epileptic spasms and neurodevelopmental delay. Epilepsy surgery remains an important treatment consideration for focal epilepsy secondary to GATOR1 variants. Favourable surgical outcomes in GATOR1-related focal epilepsy seen in 50–60% cases. Abstract: Aim: To report seizure outcomes in children with GATOR1 gene complex disorders who underwent epilepsy surgery and perform a systematic literature search to study the available evidence. Methods: The records of children with pathogenic/likely pathogenic variants in GATOR1 gene complex who underwent epilepsy surgery were reviewed. Clinical, radiological, neurophysiological, and histological data were extracted/summarized. The systematic review included all case series/reports and observational studies reporting on children or adults with genetic (germline or somatic) variants in the GATOR1 complex genes ( DEPDC5, NPRL2, NPRL3 ) with focal epilepsy with/without focal cortical dysplasia who underwent epilepsy surgery; seizure outcomes were analyzed. Results: Eight children with pathogenic/likely pathogenic variants in GATOR1 complex genes were included. All had drug-resistant epilepsy. Six children had significant neurodevelopmental delay. Epilepsy surgery was performed in all; clinical seizure freedom was noted in 4 children (50%). Systematic literature search identified 17 eligible articles; additional 30 cases with patient-level data were studied. Lesional MRI brain was seen in 80% cases. The pooled rate of seizure freedom following surgery was 60%; FCD IIa was the most encountered pathology. Interpretation: Epilepsy surgery may be effective in some children with GATOR1 complex gene variants. Seizure outcomes may be compromised by extensive epileptogenic zones.