Abstracts

Rationale: GABRA1 encodes one of the subunits of GABA-A receptor and is located on human chromosome 5q34-q35. In humans, mutations of the GABRA1 have been associated with various forms of epilepsy, ranging from mild genetic generalized epilepsies and febrile seizures. The aim of this study is to summarize the phenotypes of epilepsy in children with GABRA1 mutations. Methods: All the patients with GABRA1 heterozygous mutations were collected in the Pediatric Department of Peking University First Hospital from March 2016 to March 2019. The features of clinical manifestations, electroencephalogram, and neuroimaging were analyzed． Results: Ten patients with GABRA1 heterozygous mutations (p.L215P, p.V287I, p.R214C, p.Asn115Asp, p.Asn114Asp, p.S76R, p.Y189F, p.R214H in one patient respectively, p.R112Q in 2 patients ) were enrolled. Age at seizure onset ranged from 4 to 14 months, and the median age was 8 months. The seizure was first detected in the first year of life in 9 patients, only one patient beyond 12 months. Nine GABRA1 mutation types were identified in ten patients. One patient inherited the mutation (p.R112Q) from her mother, and the other 9 patients had de novo GABRA1 mutations. Focal seizures were observed in 8 patients, generalized tonic clonic seizures (GTCS) in 5, myoclonic seizures in 4, epileptic spasm in one patient. Multiple seizure types were observed in 8 patients. EEG showed focal discharges in 7 patients, hypsarrhythmia in one patient and a generalized photoparoxysmal response in 2 patients. Interictal EEG was normal in 2 patients. Brain MRI was normal in 10 patients. Five patients were further diagnosed with Dravet syndrome, one with West syndrome, one with unclassified early infantile epileptic encephalopathy. Seizures were exacerbated by fever or infections in 8 patients. Three patients had a history of status epilepticus during infection. Seizures in two patients were photoparoxysmal response. The last follow-up age ranging from 2.5 years to 12 years of age. Eight patients were seizure-free for 3 months to 8 years, and 2 patients still had seizures. Developmental delay was present in 8 patients with various degree. Conclusions: GABRA1-related epilepsy occurs mostly in infancy with various phenotypes. Most patients had multiple seizure types. Most patients have fever-sensitive features. Seizures can be controlled in most patients. Developmental delay is common in GABRA1-related epilepsy children. Funding: Key Research Project of the Ministry of Science and Technology of China(2016YFC0909900，2016YFC0904401)