PDF(Pubmed)
Abstract：
Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe developmental delay or regression, and those patients always fail first-line treatment with sodium channel blockers. Vitamin B6, either pyridoxine or pyridoxal 50-phosphate, has been demonstrated to improve seizure control in intractable epilepsy.
Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy.
All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed.
Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.
Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy.
All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed.
Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.
摘要：
背景：典型的KCNQ2（OMIM#602235）癫痫性脑病患者表现为新生儿早期难治性癫痫发作，伴有爆发抑制脑电图模式和严重的发育延迟或消退，这些患者的钠通道阻滞剂一线治疗总是失败。维生素B6，吡哆醇或50-磷酸吡哆醛，已被证明可以改善难治性癫痫的癫痫发作控制。
方法：这里，我们收集并总结了4例诊断为吡哆醇反应性癫痫性脑病的独立病例的临床资料，和他们的外显子组测序数据。此外，我们回顾了所有已发表的病例，并总结了临床特征，遗传变异，和吡哆醇反应性KCNQ2癫痫性脑病的治疗。
结果：四例均在新生儿期或婴儿期表现为难治性癫痫发作，伴随着全球发展的延迟。发现了KCNQ2的四种致病变体，并通过Sanger测序确认：KCNQ2[NM_172107.4：c.2312C>T（p。Thr771Ile)，c.873G>C（p。Arg291Ser)，c.652T>A（p。Trp218Arg）和c.913-915del（第Phe305del)].钠通道阻滞剂和其他抗癫痫药物未能控制其癫痫发作。大剂量吡哆醇治疗后，癫痫发作频率逐渐降低。在病例1、病例2和病例4中，吡哆醇停药后临床癫痫发作复发，恢复吡哆醇治疗后，癫痫发作再次得到控制。
结论：我们的研究表明，吡哆醇可能是KCNQ2癫痫性脑病患者的一种有希望的辅助治疗选择。
方法：这里，我们收集并总结了4例诊断为吡哆醇反应性癫痫性脑病的独立病例的临床资料，和他们的外显子组测序数据。此外，我们回顾了所有已发表的病例，并总结了临床特征，遗传变异，和吡哆醇反应性KCNQ2癫痫性脑病的治疗。
结果：四例均在新生儿期或婴儿期表现为难治性癫痫发作，伴随着全球发展的延迟。发现了KCNQ2的四种致病变体，并通过Sanger测序确认：KCNQ2[NM_172107.4：c.2312C>T（p。Thr771Ile)，c.873G>C（p。Arg291Ser)，c.652T>A（p。Trp218Arg）和c.913-915del（第Phe305del)].钠通道阻滞剂和其他抗癫痫药物未能控制其癫痫发作。大剂量吡哆醇治疗后，癫痫发作频率逐渐降低。在病例1、病例2和病例4中，吡哆醇停药后临床癫痫发作复发，恢复吡哆醇治疗后，癫痫发作再次得到控制。
结论：我们的研究表明，吡哆醇可能是KCNQ2癫痫性脑病患者的一种有希望的辅助治疗选择。
