发育性和癫痫性脑病遗传学病因及诊疗的研究进展

doi:10.16288/j.yczz.23-105

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Hereditas(Beijing) ›› 2023, Vol. 45 ›› Issue (7): 553-567.doi: 10.16288/j.yczz.23-105

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Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy

Liang Jin(), Yujie Chen, Yongjun Chen()

Department of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China

Received:2023-04-19 Revised:2023-05-21 Online:2023-07-20 Published:2023-05-31
Contact: Yongjun Chen E-mail:Jliang811@163.com;chenyj-usc@foxmail.com
Supported by:
Support by the Key Project of Hunan Provincial Health and Health Commission(20201910);“4310” Program of Clinical Medical Research of the University of South China(20224310NHYCG11)

Abstract

Abstract:

Developmental and epileptic encephalopathy (DEE) is a clinically and genetically heterogeneous group of age-dependent neurological disorders characterized by onset of refractory seizures in infancy or early childhood and affected individuals with delayed or regressive psychomotor development. With the development of next-generation sequencing technology, especially the application of whole-exome sequencing technology, more and more genes have been found to be associated with DEE.These discoveries provide a basis for the detection of pathogenic genes for DEE in clinical work, and also help to deepen our understanding of the pathogenesis of DEE. In this review, we provide a comprehensive review of the genetic etiology, diagnosis and treatment of DEE, in order to assist clinicians in early identification of relevant gene mutations, thereby expediting disease diagnosis and timely implementation of optimal treatment.

Key words: genetic variation, DEE, OMIM database

Liang Jin, Yujie Chen, Yongjun Chen. Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy[J]. Hereditas(Beijing), 2023, 45(7): 553-567.

Figures/Tables 4

Fig. 1

Table 1

Fig. 2

Table 2

Epilepsy syndromes associated with DEE"

癫痫综合征	癫痫发作特点	发病时期	相关变异基因(例)	发育特点
早期肌阵挛性脑病 (early myoclonic encephalopathy，EME)	顽固性肌阵挛性癫痫发作和严重早期脑病	出生后前 2个月	ERBB4	可发展为小头畸形，严重的发育迟缓
大田原综合征 (Ohtahara syndrome，OS)	强直性癫痫发作占主导地位，肌阵挛性癫痫发作不常见	1~3个月	SCN2A、CDKL5、 SLC25A22	可发展为小头畸形，严重的发育迟缓
婴儿痉挛症(West syndrome，WS)	癫痫发作性痉挛	3~12个月	ARX、GRIN2B、SPTAN1、STXBP1	整体发育障碍(伴或不伴消退)通常见于癫痫发作时。偶尔发育可能是正常的
Dravet综合征(Dravet syndrome，DS)	大约60%的病例中，第一次癫痫发作与发烧有关	6个月左右	SCN1A	共济失调和锥体体征可能出现，发育可能消退
婴儿期癫痫伴有迁移性局灶性癫痫发作(epilepsy of infancy with migrating focal seizures，EIMFS)	出生后第一年出现难治性局灶性癫痫发作，伴有严重的脑病	出生后前 6个月	KCNT1、ATP7A、SCN2A	可发展为小头畸形，可发育延迟
非进展性疾病中的肌阵挛性脑病(myoclonic encephalopathy in non- progressive disorders，MENPD)	反复发作的肌阵挛性癫痫持续状态	出生后前 5年	DHDDS	通常可见严重的神经和发育障碍
Lennox-Gastaut综合征(Lennox- Gastaut syndrome，LGS)	多种类型的难治性癫痫发作	1~7岁	CHD2	通常可见发育停滞或消退
癫痫性脑病伴睡眠期间持续性棘波(epileptic encephalopathy with continuous spike-and-wave during sleep，CSWS)	睡眠期间连续的尖波及癫痫发作	2~12岁	CDKL5	认知、行为和精神功能的进行性下降
Landau Kleffner综合征(Landau Kleffner syndrome，LKS)	癫痫发作可在预测的年龄自发缓解	2~8岁	GRIN2A	既往发育和认知正常的儿童中亚急性发作的获得性失语症

Table 2

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编码的蛋白功能	功能亚分类	发育性和癫痫性脑病基因(OMIM收录)
离子通道	电压门控钠通道	SCN1A、SCN1B、SCN2A、SCN3A、SCN8A
	电压门控钾通道	KCNA2、KCNB1、KCNC2、KCNQ2、KCNT1、KCNT2
	电压门控钙通道	CACNA1A、CACNA1E、CACNA2
	配体门控离子通道GABA受体	GABRA1、GABRA2、GABRA5、GABRB1、GABRB2、GABRB3、GABRG2、GABBR2
	配体门控离子通道谷氨酸受体	FRRS1L、GRIN1、GRIN2B、GRIN2D
	HCN通道	HCN1
膜运输调节		STX1B、STXBP1、CPLX1、NSF、SLC1A2、AP3B2、NAPB
酶/酶调节剂	蛋白质/氨基酸代谢酶	ALG13、CDKL5、PIGA、PIGB、PIGP、PIGQ、SIK1、ST3GAL3、SYNJ1、PIGS、FBXO28、GLS、UFSP2、PARS2
	核酸代谢酶	PNKP、AARS1、ITPA、CAD、CHD2
	能量代谢酶	MDH2、GOT2、MDH1
	信号转导酶	PLCB1、GNAO1、RHOBTB2
	酶调节剂	PHACTR1、ARHGEF9、TBC1D24、DOCK7、CYFIP2
	其他	ADAM22、PPP3CA、UGP2、UGDH、GAD1、DNM1、CDK19、UBA5
转运蛋白	氨基酸转运蛋白	SLC25A22、SLC25A12、SLC38A3
	阴/阳离子转运蛋白	SLC13A5、SLC12A5、ATP6V1A、ATP1A2、ATP1A3、ATP6V0A1
	核苷酸-糖转运蛋白	SLC35A2
细胞骨架蛋白		SPTAN1、ACTL6B
细胞代谢及信号转导		ARX、WWOX、FGF12、FGF13、DMXL2、SZT2、NTRK2、YWHAG
细胞粘附分子		PCDH19
核酸结合蛋白		CUX2、NEUROD2、GUF1、HNRNPU、SMC1A、CELF2、EEF1A2
分子伴侣		CNPY3
不明确		NECAP1、DENND5A、PACS2、TRAK1、RNF13、DALRD3、HID1、MAST3、FZR1

Advances in genetic etiology, diagnosis and treatment of developmental and epileptic encephalopathy

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