LAUSR

OBJECTIVES To summarize the clinical features of epilepsy related to DEPDC5, NPRL2, and NPRL3 genes encoding the GATOR1 complex in children, and to evaluate the factors affecting the prognosis of these epilepsies. METHODS In this retrospective study, we reviewed the clinical and genetic characteristics of children with epilepsy related to GATOR1 variants who were admitted to the Peking University First Hospital between January 2016 and December 2021. Potential prognostic factors were assessed by comparing children with and without ongoing seizures. RESULTS Fifty probands, including 31 boys and 19 girls were recruited. The median age at onset of epilepsy was 4 months, and 64% of patients had early-onset epilepsy (≤1 year). The most frequent epileptic seizure type was focal seizure (86%). Among the 50 patients, only 6 were with de novo variants. According to the novel classification framework for GATOR1 variants, 36 patients were with pathogenic variants and 14 with likely pathogenic variants. DEPDC5 variants were found in 37 patients, NPRL3 in 9, and NPRL2 in 4. The phenotype was similar among the probands, with variants in DEPDC5, NRPL2, or NPRL3 respectively. 76% (38/50) epilepsy related to GATOR1 complex gene variants were neuroimaging positive, including Brain MRI positive in 31 patients, and MRI combined FDG-PET positive in the other 7 patients. Twenty-seven patients underwent epilepsy surgery. In total, after initial anti-seizure medications alone, 92% (46/50) patients were drug-resistant epilepsies, only 8% (4/50) of the probands became seizure-free but seizure-free (≥6m) occurred in 92.6% (25/27) of patients with drug-resistant epilepsy after epilepsy surgery at the last follow-up. Patients undergoing epilepsy surgery had better epilepsy prognosis. SIGNIFICANCE Epilepsy related to GATOR1 complex gene variant had high possibility to be drug-resistant epilepsy and to have positive neuroimaging finding. Epilepsy surgery is the only favorable factor for better seizure prognosis in this kind epilepsy.