Background

FGF12 (FHF1) gene encodes voltage-gated sodium channel (Nav)-binding protein fibroblast growth factor homologous factor 1, which could cause seizures by regulating voltage dependence of Nav fast inactivation and neuron excitability. The most common pathogenic variant FGF12 c.341G > A related early-onset epileptic encephalopathies (EOEE) was characterized by intractable seizures and developmental disabilities.

Results

Using whole exome sequencing, a de novo hotspot variant c.341G > A (NM_021032.4) of FGF12 was identified in three unrelated EOEE probands. All probands were seizure free after a combination treatment of valproic acid (VPA) and topiramate (TPM). The motor and cognitive skills in two probands were improved due to the early and effective treatment. In order to compare the effectiveness of different treatment strategies for the disease, a review of treatments for FGF12-related epilepsy was made.

Conclusion

We reported three FGF12 c.341G > A related EOEE patients responded well to a combination antiepileptic therapy of VPA and TPM. The current study is the first to describe the combination therapy of VPA and TPM in FGF12 c.341G > A related EOEE patients. This study may contribute to future medication consultation for intractable epilepsy with FGF12 hotspot variants.

中文翻译：

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FGF12相关早发性癫痫性脑病患者的有效治疗

背景

FGF12 ( FHF1 ) 基因编码电压门控钠通道 (Nav) 结合蛋白成纤维细胞生长因子同源因子 1，可通过调节 Nav 快速失活和神经元兴奋性的电压依赖性引起癫痫发作。最常见的致病性变异FGF12 c.341G > A 相关的早发性癫痫性脑病 (EOEE) 的特征是顽固性癫痫发作和发育障碍。

结果

使用全外显子组测序，在三个不相关的 EOEE 先证者中鉴定出FGF12的从头热点变体 c.341G > A (NM_021032.4) 。在丙戊酸 (VPA) 和托吡酯 (TPM) 联合治疗后，所有先证者均无癫痫发作。由于早期有效的治疗，两名先证者的运动和认知技能得到了改善。为了比较不同治疗策略对该疾病的有效性，对FGF12相关癫痫的治疗进行了回顾。

结论

我们报道了三名FGF12 c.341G > A 相关的 EOEE 患者对 VPA 和 TPM 的联合抗癫痫治疗反应良好。本研究首次描述了 VPA 和 TPM 联合治疗FGF12 c.341G > A 相关的 EOEE 患者。这项研究可能有助于未来对具有FGF12热点变异的难治性癫痫的药物咨询。