Institut de Recherches Servier, Rue Francis Perrin, 91190 Gif-sur-Yvette, France.
Cells. 2024 Oct 24;13(21):1763. doi: 10.3390/cells13211763.
Developmental and Epileptic Encephalopathies (DEEs) represent a clinically and genetically heterogeneous group of rare and severe epilepsies. DEEs commonly begin early in infancy with frequent seizures of various types associated with intellectual disability and leading to a neurodevelopmental delay or regression. Disease-causing genomic variants have been identified in numerous genes and are implicated in over 100 types of DEEs. In this context, genes encoding voltage-gated ion channels (VGCs) play a significant role, and part of the large phenotypic variability observed in DEE patients carrying VGC mutations could be explained by the presence of genetic modifier alleles that can compensate for these mutations. This review will focus on the current knowledge of the compensatory effect of DEE-associated voltage-gated ion channels and their therapeutic implications in DEE. We will enter into detailed considerations regarding the sodium channels SCN1A, SCN2A, and SCN8A; the potassium channels KCNA1, KCNQ2, and KCNT1; and the calcium channels CACNA1A and CACNA1G.
发育性和癫痫性脑病（DEEs）是一组临床上和遗传上具有异质性的罕见且严重的癫痫。DEEs 通常在婴儿期早期发病，频繁出现各种类型的癫痫发作，伴有智力残疾，并导致神经发育迟缓或倒退。在许多基因中已经发现了导致疾病的基因组变异体，这些变异体与 100 多种 DEE 有关。在这种情况下，编码电压门控离子通道（VGCs）的基因起着重要作用，携带 VGC 突变的 DEE 患者中观察到的部分大的表型变异性可以通过存在遗传修饰等位基因来解释，这些等位基因可以补偿这些突变。本综述将重点介绍与 DEE 相关的电压门控离子通道的补偿作用及其在 DEE 中的治疗意义。我们将详细考虑钠通道 SCN1A、SCN2A 和 SCN8A；钾通道 KCNA1、KCNQ2 和 KCNT1；以及钙通道 CACNA1A 和 CACNA1G。
