TY -的T1 -单基因的癫痫病JF -神经学乔-神经病学SP - 817 LP 首页- 831 - 10.1212 / WNL。0000000000012744六世- 97 - 17盟左伦Guerrini AU -西蒙娜Balestrini AU -伊莱恩·c·Wirrell盟马修·c·沃克Y1 - 2021/10/26 UR - //www.ez-admanager.com/content/97/17/817.abstract首页 N2 -一个单基因的病因可以确定在多达40%的患有严重的癫痫。解决更早和更合适的治疗策略,临床医生需要知道特定基因造成的影响可能在病理生理学、自然历史、并发症、治疗选择。在这个叙述审查中,我们总结的概念基于潜在的病理生理机制的遗传癫痫治疗方案和现在的当前知识基于对照试验或较低的研究提供的证据分类的证据。总体而言,证据足够健壮指导抗癫痫药物(ASM)选择遗传癫痫仍局限于更频繁的条件对照试验和观察性研究是不可能的。多数单基因疾病是非常罕见的和ASM的选择对他们来说仍然是基于推断来自于观察性研究和早期,经常轶事,经验与精确治疗。精密医学仍然是只适用于狭窄的单基因的癫痫病患者,可能目标的实际功能缺陷。表型异质性是非凡的,通过他们的发展影响,一些基因突变激活epileptogenesis产后可能无法逆转。其他基因似乎兴奋性纯功能性的后果,代理通过功能损失或影响,而这些可能相反的治疗意义。此外,错义突变的功能后果很难预测,使精度比估计确定的治疗方法更为复杂的解释。 Knowledge of genetic etiologies can influence the approach to surgical treatment of focal epilepsies. Identification of germline mutations in specific genes contraindicates surgery while mutations in other genes do not. Identification, quantification, and functional characterization of specific somatic mutations before surgery using CSF liquid biopsy or after surgery in brain specimens will likely be integrated in planning surgical strategies and reintervention after a first unsuccessful surgery as initial evidence suggests that mutational load may correlate with the epileptogenic zone. Promising future directions include gene manipulation by DNA or mRNA targeting; although most are still far from clinical use, some are in early phase clinical development.ASM=antiseizure medication; ASO=antisense oligonucleotide; DEE=developmental epileptic encephalopathy; DS=Dravet syndrome; EE=epileptic encephalopathy; FCD=focal cortical dysplasia; mTOR=mammalian target of rapamycin; mTORC1=mammalian target of rapamycin complex 1; NAFE=nonacquired focal epilepsy; PCDH19-GCE=PCDH19 girls-clustering epilepsy; siRNA=small interfering RNA; TANGO=targeted augmentation of nuclear gene output; TSC=tuberous sclerosis complex ER -