我们报告了一个在四个月大时发展为肌阵挛性癫痫持续状态(MSE)的儿童,与有节奏的高振幅delta和叠加的(多)尖峰(RHADS)相关,具有GABRB2(GABAA受体的β2亚基)变体。该患者在新生儿发病Alpers综合征(AS)的推定诊断下接受治疗,并接受了POLG1(聚合酶γ1)的靶向序列分析和随后的全外显子组序列分析(WES)。病人目前是10岁,八个月大的男孩,患有与RHADS相关的每日MSE和婴儿期早期严重的全球发育迟缓。尽管POLG1突变为阴性,WES揭示了GABRB2的从头错义变体(NM_021911.2:c.784G>T,p.[Val262Phe]).基于对GABRB2变体案例系列的回顾,我们发现18例病例中有5例具有与我们患者相关的临床和脑电图特征.总之,这种从头GABRB2变体与AS表型相关,以抗治疗MSE和RHADS为特征,并且可能代表无POLG1突变的新生儿发病AS的替代病因[随视频序列发布]。
We report a child who developed myoclonic status epilepticus (MSE) at four months of age, associated with rhythmic high-amplitude delta and superimposed (poly) spikes (RHADS), harbouring a GABRB2 (β2 subunit of the GABA A receptor) variant. The patient was treated under a presumptive diagnosis of neonatal-onset Alpers syndrome (AS) and underwent targeted sequence analysis for
POLG1 (polymerase gamma 1) and subsequent whole-exome sequence analysis (WES). The patient is currently a 10-year, eight-month-old boy, suffering from daily MSE associated with RHADS and severe global developmental delay from early infancy. Although
POLG1 mutation was negative, WES revealed a de novo missense variant of GABRB2 (NM_021911.2: c.784G>T, p.[Val262Phe]). Based on a review of case series with GABRB2 variants, we found that five of the 18 cases shared the clinical and EEG characteristics associated with our patient. In summary, this de novo GABRB2 variant was associated with an AS phenotype, characterized by treatment-resistant MSE and RHADS, and may represent an alternative aetiology for neonatal-onset AS without
POLG1 mutation [Published with video sequence].