Research progress of ADPRHL2 gene related stress-induced childhood-onset neurodegeneration with variable ataxia and seizures / 中华实用儿科临床杂志

Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures caused by ADPRHL2 gene mutation is a recently diagnosed hereditary neurodegenerative disease, featured by a small number of reported cases, early age of onset, and high mortality.Therefore, to attract the attention of clinicians, the research progress of ADPRHL2 gene, its protein structure and function, as well as the hereditary mode, pathogenic mechanism, clinical features, and treatment prognosis of stress-induced childhood-onset neurodegeneration with variable ataxia and seizures were reviewed in this paper.

Developmental epileptic encephalopathy associated with the CACNA1E gene mutation / 中华实用儿科临床杂志

One of the important causes of developmental epileptic encephalopathy (DEE) is the mutation of ion channel genes, including the mutation of the CACNA1E gene. CACNA1E-related DEE cases were first reported in 2018.The mutation types include new missense mutations, nonsense mutations and frameshift mutations, but the correlation between mutation sites and types with the phenotype of DEE is not clear.This review aims to summarize the reported CACNA1E-related DEE cases, and explore the correlation between the clinical phenotype of CACNA1E-related DEE and gene mutation sites and mutation types.Meanwhile, possible pathogenesis of CACNA1E-related DEE and the progress of drug intervention were reviewed to provide references for the diagnosis and precise treatment of DEE.

Clinical phenotypes of epilepsy associated with GABRA1 gene variants / 中华儿科杂志

Objective@#To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants.@*Methods@#A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively.@*Results@#A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient′s mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication.@*Conclusions@#In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.