Srivastava Siddharth, Sahin Mustafa
Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115 USA.
J Neurodev Disord. 2017 Jun 23;9:23. doi: 10.1186/s11689-017-9202-0. eCollection 2017.
Epileptic encephalopathies represent a particularly severe form of epilepsy, associated with cognitive and behavioral deficits, including impaired social-communication and restricted, repetitive behaviors that are the hallmarks of autism spectrum disorder (ASD). With the advent of next-generation sequencing, the genetic landscape of epileptic encephalopathies is growing and demonstrates overlap with genes separately implicated in ASD. However, many questions remain about this connection, including whether epileptiform activity itself contributes to the development of ASD symptomatology. In this review, we compiled a database of genes associated with both epileptic encephalopathy and ASD, limiting our purview to Mendelian disorders not including inborn errors of metabolism, and we focused on the connection between ASD and epileptic encephalopathy rather than epilepsy broadly. Our review has four goals: to (1) discuss the overlapping presentations of ASD and monogenic epileptic encephalopathies; (2) examine the impact of the epilepsy itself on neurocognitive features, including ASD, in monogenic epileptic encephalopathies; (3) outline many of the genetic causes responsible for both ASD and epileptic encephalopathy; (4) provide an illustrative example of a final common pathway that may be implicated in both ASD and epileptic encephalopathy. We demonstrate that autistic features are a common association with monogenic epileptic encephalopathies. Certain epileptic encephalopathy syndromes, like infantile spasms, are especially linked to the development of ASD. The connection between seizures themselves and neurobehavioral deficits in these monogenic encephalopathies remains open to debate. Finally, advances in genetics have revealed many genes that overlap in ties to both ASD and epileptic encephalopathy and that play a role in diverse central nervous system processes. Increased attention to the autistic features of monogenic epileptic encephalopathies is warranted for both researchers and clinicians alike.
癫痫性脑病是一种特别严重的癫痫形式，与认知和行为缺陷相关，包括社交沟通障碍以及自闭症谱系障碍（ASD）的标志性特征——受限的重复行为。随着下一代测序技术的出现，癫痫性脑病的遗传图谱不断扩展，并显示出与分别涉及ASD的基因存在重叠。然而，关于这种联系仍有许多问题，包括癫痫样活动本身是否会导致ASD症状的发展。在本综述中，我们编制了一个与癫痫性脑病和ASD相关的基因数据库，将范围限制在不包括先天性代谢缺陷的孟德尔疾病上，并且我们关注的是ASD与癫痫性脑病之间的联系，而不是广义上的癫痫。我们的综述有四个目标：（1）讨论ASD和单基因癫痫性脑病的重叠表现；（2）研究癫痫本身对单基因癫痫性脑病中神经认知特征（包括ASD）的影响；（3）概述导致ASD和癫痫性脑病的许多遗传原因；（4）提供一个可能与ASD和癫痫性脑病都有关的最终共同途径的示例。我们证明自闭症特征与单基因癫痫性脑病常见相关。某些癫痫性脑病综合征，如婴儿痉挛症，尤其与ASD的发展有关。在这些单基因脑病中，癫痫发作本身与神经行为缺陷之间的联系仍存在争议。最后，遗传学的进展揭示了许多与ASD和癫痫性脑病都有关联且在多种中枢神经系统过程中起作用的基因。研究人员和临床医生都有必要更加关注单基因癫痫性脑病的自闭症特征。
