Specchio Nicola, Di Micco Valentina, Trivisano Marina, Ferretti Alessandro, Curatolo Paolo
Rare and Complex Epilepsy Unit, Division of Neurology, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy.
Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, Italy.
Epilepsia. 2022 Jan;63(1):6-21. doi: 10.1111/epi.17115. Epub 2021 Nov 6.
Autism spectrum disorder (ASD) is frequently associated with infants with epileptic encephalopathy, and early interventions targeting social and cognitive deficits can have positive effects on developmental outcome. However, early diagnosis of ASD among infants with epilepsy is complicated by variability in clinical phenotypes. Commonality in both biological and molecular mechanisms have been suggested between ASD and epilepsy, such as occurs with tuberous sclerosis complex. This review summarizes the current understanding of causal mechanisms between epilepsy and ASD, with a particularly genetic focus. Hypothetical explanations to support the conjugation of the two conditions include abnormalities in synaptic growth, imbalance in neuronal excitation/inhibition, and abnormal synaptic plasticity. Investigation of the probable genetic basis has implemented many genes, although the main risk supports existing hypotheses in that these cluster to abnormalities in ion channels, synaptic function and structure, and transcription regulators, with the mammalian target of rapamycin (mTOR) pathway and "mTORpathies" having been a notable research focus. Experimental models not only have a crucial role in determining gene functions but are also useful instruments for tracing disease trajectory. Precision medicine from gene therapy remains a theoretical possibility, but more contemporary developments continue in molecular tests to aid earlier diagnoses and better therapeutic targeting.
自闭症谱系障碍（ASD）常与患有癫痫性脑病的婴儿相关，针对社交和认知缺陷的早期干预可对发育结果产生积极影响。然而，癫痫婴儿中ASD的早期诊断因临床表型的变异性而变得复杂。ASD和癫痫之间在生物学和分子机制上存在共性，如结节性硬化症复合体的情况。本综述总结了目前对癫痫和ASD之间因果机制的理解，尤其侧重于遗传学方面。支持这两种病症关联的假设性解释包括突触生长异常、神经元兴奋/抑制失衡以及异常的突触可塑性。对可能的遗传基础的研究已涉及许多基因，尽管主要风险支持现有假设，即这些基因集中在离子通道、突触功能和结构以及转录调节因子的异常上，其中雷帕霉素哺乳动物靶标（mTOR）途径和“mTOR病”一直是显著的研究重点。实验模型不仅在确定基因功能方面具有关键作用，也是追踪疾病轨迹的有用工具。基因治疗的精准医学仍然是一种理论上的可能性，但分子检测方面的更多当代进展仍在继续，以帮助早期诊断和更好地进行治疗靶向。
