Effective treatments for FGF12-related early-onset epileptic encephalopathies patients

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. (c) 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.