Department of Neurology, Université Libre de Bruxelles, Hôpital Erasme, Brussels, Belgium.
Curr Opin Neurol. 2013 Apr;26(2):137-45. doi: 10.1097/WCO.0b013e32835f19da.
Genetic epilepsies in childhood are a complex group of disorders, with heterogeneous etiologies and clinicopathologic features. This review focuses on primary genetic epilepsies, which may have variable neuropsychiatric comorbidities, but usually have no underlying gross neuropathology or evident metabolic disturbance. Epilepsy due to inherited metabolic diseases, chromosomal abnormalities, phakomatoses, or malformations of cortical development is reviewed elsewhere.
The use of high-throughput approaches to sequence DNA and to detect copy number variants is revealing a landscape of mutations in genetic epilepsies, affecting a variety of genes involved in neuronal excitability, synaptic transmission, neuronal metabolism, or network development.
A number of distinct clinical syndromes of pediatric genetic epilepsy have been described and linked to specific gene defects. Phenotypes may include, in addition to epilepsy, variable degrees of intellectual disability, elements of autism spectrum disorders, other psychiatric disorders, and motor impairment. In some cases, these comorbidities derive from uncontrolled seizure activity (epileptic encephalopathies), but in other cases they are direct, multifaceted consequences of global brain dysfunction. Mutations may be de novo, or, when inherited, show reduced penetrance and variable expressivity. Understanding the genetics of these conditions will improve diagnosis, reveal pathogenic mechanisms, and eventually lead to better treatment.
儿童遗传性癫痫是一组具有复杂病因和临床病理特征的疾病。本综述重点介绍原发性遗传性癫痫，其可能存在多种神经精神共病，但通常无明显的大体神经病理学或代谢紊乱。遗传性代谢疾病、染色体异常、神经皮肤综合征或皮质发育畸形引起的癫痫在其他地方进行了综述。
高通量方法用于 DNA 测序和拷贝数变异检测，揭示了遗传性癫痫中的突变图谱，涉及多种参与神经元兴奋性、突触传递、神经元代谢或网络发育的基因。
已经描述了多种不同的儿童遗传性癫痫临床综合征，并与特定的基因缺陷相关。除了癫痫之外，表型还可能包括不同程度的智力障碍、自闭症谱系障碍的元素、其他精神障碍和运动障碍。在某些情况下，这些共病是由不受控制的癫痫发作（癫痫性脑病）引起的，但在其他情况下，它们是大脑整体功能障碍的直接、多方面的后果。突变可能是新生的，或者当遗传时，表现为低外显率和可变表达。了解这些疾病的遗传学将改善诊断、揭示发病机制，并最终导致更好的治疗。
