Background: CSNK2B deficiency underlies the pathogenesis of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). In this study, we present four cases of pediatric seizures caused by de novo variants in CSNK2B, with the aim to reinforce the clinical and variant data pertaining to early genetic factors associated with epilepsy.

Methods: Trio whole exome sequencing were used to detect variants in the proband and her family members, and bioinformatics annotation was performed for the variant. Sanger sequencing and CSNK2B cDNA sequencing were employed to ascertain the carrier status of additional family members and evaluate the potential impact of variants on splicing.

Results: All four cases presented with epilepsy as the initial manifestation, accompanied by global developmental delay, particularly in language and motor developmental delay. Cases 1, 3 and 4 exhibited full-scale tonic-clonic seizures, while case 2 displayed myoclonic and typical absence seizures. Furthermore, case 2 demonstrated delayed growth and development compared to age-matched peers. No abnormality was detected in the head magnetic resonance imaging (MRI). Genetic analysis revealed novel heterozygous variants in the CSNK2B gene in all four cases, including c.175 + 1G > A, c.73-2A > G, c.291 + 1G > A and c.481delA. In case 2, reverse transcription analysis of CSNK2B mRNA revealed the retention of the 3' end sequence of Intron 2 and deletion of the 5' end sequence of Exon 3. In treatment, four case received a combination of one to three types of antiseizure medication and rehabilitation training individually. Case 1 continued to experience seizures to varying degrees, while cases 2-4 demonstrated effective seizure control. Overall motor and intellectual development improved in all four cases, however, there was slow recovery in language function.

Conclusion: This study elucidates the molecular etiology of epilepsy in four cases with POBINDS and expands the mutational spectrum of pathogenic variants in the CSNK2B, highlighting their impact on splicing. The highly genetic heterogeneous phenotype of POBINDS relies on the detection of pathogenic variants in CSNK2B. Conventional antiseizure medication effectively control seizures, while rehabilitation treatment can significantly improve intelligence and motor function to varying degrees; however, language recovery tends to be relatively slow.

Keywords: CSNK2B; Epilepsy; Poirier-Bienvenu neurodevelopmental syndrome; Whole exome sequencing; cDNA sequencing.

© 2025. The Author(s).

背景： CSNK2B 缺乏是 Poirier-Bienvenu 神经发育综合征（POBINDS）发病机制的基础。在这项研究中，我们介绍了四个由 CSNK2B 中新生变异引起的儿科癫痫病例，旨在加强与早期遗传因素相关的临床和突变数据，这些因素与癫痫有关。

方法： 使用三联体全外显子测序来检测受检者及其家庭成员中的变异，并对变异进行生物信息学注释。采用 Sanger 测序和 CSNK2B cDNA 测序，以确定其他家庭成员的携带状态并评估突变对剪接的潜在影响。

结果： 所有四个病例均以癫痫为首发表现，并伴有全面发育迟缓，特别是语言和运动发育迟缓。案例 1、3 和 4 展现了全范围强直-阵挛性发作，而案例 2 显示肌阵挛性和典型失神发作。此外，案例 2 的生长和发展明显落后于同龄人。头颅磁共振成像（MRI）未发现异常。基因分析在所有四个病例中发现了 CSNK2B 基因中的新杂合突变，包括 c.175 + 1G > A、c.73-2A > G、c.291 + 1G > A 和 c.481delA。在案例 2 中，CSNK2B mRNA 的反转录分析显示第 2 内含子的 3' 端序列保留，并且第 3 外显子的 5' 端序列缺失。治疗方面，四个病例分别接受了一到三种抗癫痫药物和康复训练的组合疗法。案例 1 继续不同程度地经历发作，而案例 2-4 表现出有效的发作控制。总体而言，所有四个病例的手动能力和智力发展都有所改善，但语言功能恢复较慢。

结论： 本研究阐明了 POBINDS 四个病例中癫痫的分子病因，并扩展了 CSNK2B 致病变异突变谱，强调其对剪接的影响。POBINDS 高度遗传异质性表型依赖于在 CSNK2B 中检测到致病变异。常规抗癫痫药物可以有效控制发作，而康复治疗可以在不同程度上显著改善智力和运动功能；然而，语言恢复往往相对较慢。

关键词： CSNK2B；癫痫；Poirier-Bienvenu 神经发育综合征；全外显子测序；cDNA 测序。