Lo-Castro Adriana, Curatolo Paolo
Neuroscience Department, Pediatric Neurology and Psychiatry Unit, Tor Vergata University of Rome, Italy.
Neuroscience Department, Pediatric Neurology and Psychiatry Unit, Tor Vergata University of Rome, Italy.
Brain Dev. 2014 Mar;36(3):185-93. doi: 10.1016/j.braindev.2013.04.013. Epub 2013 May 29.
Autism Spectrum Disorders (ASDs) and Attention Deficit and Hyperactivity Disorder (ADHD) are the most common comorbid conditions associated with childhood epilepsy. The co-occurrence of an epilepsy/autism phenotype or an epilepsy/ADHD phenotype has a complex and heterogeneous pathogenesis, resulting from several altered neurobiological mechanisms involved in early brain development, and influencing synaptic plasticity, neurotransmission and functional connectivity. Rare clinically relevant chromosomal aberrations, in addition to environmental factors, may confer an increased risk for ASDs/ADHD comorbid with epilepsy. The majority of the candidate genes are involved in synaptic formation/remodeling/maintenance (NRX1, CNTN4, DCLK2, CNTNAP2, TRIM32, ASTN2, CTNTN5, SYN1), neurotransmission (SYNGAP1, GABRG1, CHRNA7), or DNA methylation/chromatin remodeling (MBD5). Two genetic disorders, such as Tuberous sclerosis and Fragile X syndrome may serve as models for understanding the common pathogenic pathways leading to ASDs and ADHD comorbidities in children with epilepsy, offering the potential for new biologically focused treatment options.
自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）是与儿童癫痫相关的最常见的共病情况。癫痫/自闭症表型或癫痫/ADHD表型的同时出现具有复杂且异质性的发病机制，这是由早期大脑发育中涉及的几种神经生物学机制改变所导致的，并影响突触可塑性、神经传递和功能连接。除环境因素外，罕见的临床相关染色体畸变可能会增加ASD/ADHD与癫痫共病的风险。大多数候选基因参与突触形成/重塑/维持（NRX1、CNTN4、DCLK2、CNTNAP2、TRIM32、ASTN2、CTNTN5、SYN1）、神经传递（SYNGAP1、GABRG1、CHRNA7）或DNA甲基化/染色质重塑（MBD5）。两种遗传疾病，如结节性硬化症和脆性X综合征，可作为理解导致癫痫儿童ASD和ADHD共病的常见致病途径的模型，为新的以生物学为重点的治疗选择提供了可能性。
