BACKGROUND Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3 months of birth and severe interictal epileptiform discharge, including burst suppression. This study assessed the utility of targeted gene panel sequencing in the genetic diagnosis of this disease. MATERIALS AND METHODS Targeted gene panel sequencing was performed in 150 early infantile-onset DEE patients (≤3 months of age), and we extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. RESULTS Of the early infantile-onset DEE patients, 70 were neonatal-onset DEE and the other 80 patients began experiencing seizures from 1 to 3 months after birth. There were 11 different pathogenic or likely pathogenic variants among 34.7% (52/150) of patients with early infantile-onset DEE, in whom KCNQ2, STXBP1, CDKL5, and SCN1A were the major pathogenic variants. Among the neonatal-onset DEE patients, pathological genes were identified in 42.9% (30/70), indicating a significantly higher diagnostic yield than in 27.5% (22/80) of patients who experienced seizure onset 1 to 3 months after birth (p = 0.048). Among the neonatal-onset DEE group, variants in KCNQ2, STXBP1, and CDKL5 were detected at high frequencies, accounting for 66.7% (20/30) of the pathogenic or likely pathogenic variants found in this study. CONCLUSION Targeted gene panel sequencing demonstrated a high yield of pathogenic variants in the diagnosis of early-onset epileptic encephalopathy, especially in those with neonatal-onset DEE. Early diagnosis of early-onset epileptic encephalopathy may improve the prognosis of patients by earlier selection of appropriate treatment based on pathogenic variant.

中文翻译：

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婴儿早期发病的发育性和癫痫性脑病的靶向基因组测序

背景早发性发育性和癫痫性脑病 (DEE) 的特征是在出生后 3 个月内开始反复发作和严重的发作间期癫痫样放电，包括爆发抑制。本研究评估了靶向基因组测序在该疾病的遗传诊断中的效用。材料和方法 在 150 名婴儿早期发病的 DEE 患者（≤ 3 个月大）中进行了靶向基因组测序，我们根据基因型广泛审查了他们的临床特征，包括治疗效果。结果 早期婴儿型 DEE 患者中，70 例为新生儿型 DEE，另外 80 例患者在出生后 1 至 3 个月开始出现癫痫发作。在 34 个中，有 11 个不同的致病性或可能致病性变异。7% (52/150) 的早期婴儿型 DEE 患者，其中 KCNQ2、STXBP1、CDKL5 和 SCN1A 是主要的致病变异。在新生儿起病的 DEE 患者中，42.9% (30/70) 的病理基因被识别，表明诊断率明显高于出生后 1 至 3 个月癫痫发作的 27.5% (22/80) 患者 (p = 0.048）。在新生儿发病的 DEE 组中，高频率检测到 KCNQ2、STXBP1 和 CDKL5 的变异，占本研究发现的致病或可能致病变异的 66.7% (20/30)。结论 靶向基因组测序证明在早发性癫痫性脑病的诊断中致病变异的产量很高，尤其是在新生儿发病的 DEE 患者中。