The Clinical Phenotypes and Genetics in Pediatric Epilepsy Patients with GATOROpathy
Abstract number :
2.078
Submission category :
4. Clinical Epilepsy / 4A. Classification and Syndromes
Year :
2021
Submission ID :
1826451
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:54 AM
Authors :
Donghwa Yang, - National Health Insurance Service Ilsan Hospital; Hoon-Chul Kang – Yonsei University College of Medicine; Heung Dong Kim – Yonsei University College of Medicine; Joon soo Lee – Yonsei University College of Medicine; Se Hee Kim – Yonsei University College of Medicine
Rationale: DEPDC5 (DEP domain containing protein 5), with NPRL2 and NPRL3 (nitrogen permease regulator-like 2 and 3) from the GATOR1 (GAP activity towards rags complex 1) complex have an important function of negative regulator in the mechanistic target of rapamycin complex 1 (mTORC1) pathway. GATORopathies with variants in DEPDC5, NPRL2, and NPRL3 are known to result in various focal epilepsy. This study aimed to study the clinical phenotypes and genetics in pediatric epilepsy patients with GATORopathy.
Methods: This study retrospectively analyzed medical records of epilepsy patients related variants in GATOR1 encoding genes (DEPDC5, NPRL2, and NPRL3) using targeted gene panel for brain tissue or whole blood samples from 2006 to 2020 at Severance Children's hospital.
Results: We identified 17 epilepsy patients with GATORopathy (including 12 DEPDC variants, 1 NPRL2 variant, and 4 NPRL3 variants). Eight (47.1%) patients were boys. The median seizure onset age was 3.4 (IQR, 0.3 – 43.8) months. Nine of the total patients were unable to control their seizures, and finally underwent epilepsy surgery (7 DEPDC5 and 2 NPRL3 variants). Five of total 17 (29.4%) patients began first seizure in neonatal period, all of whom underwent epilepsy surgery. Of the 9 patients who performed epilepsy surgery, three did not show any specific findings in the first evaluation of the brain MRI. The epilepsy phenotypes varied from febrile seizure to spasms, sleep-related hypermotor epilepsy, and frontal lobe epilepsy (spasms: 35%, sleep-related hypermotor epilepsy 20%). Of the 9 patients who underwent epilepsy surgery, Six patients showed poor prognosis for relapse or uncontrolled seizure after surgery (Among 9 patients, FCDIIa pathology were the most common).
Conclusions: This study suggested that the various phenotypes of GATORopathy in pediatric epilepsy patients vary from mild febrile seizure to severe focal cortical dysplasia.
Funding: Please list any funding that was received in support of this abstract.: I have no funding.
Clinical Epilepsy