Molecular Neurogenetics Unit, IRCCS Foundation Carlo Besta Neurological Institute, Via L. Temolo 4, 20126, Milan, Italy.
Department of Pediatric Neurology, IRCCS Foundation Carlo Besta Neurological Institute, Via Celoria 11, 20131, Milan, Italy.
Curr Neurol Neurosci Rep. 2017 Oct 30;17(12):97. doi: 10.1007/s11910-017-0806-2.
Hyperkinetic movement disorders can manifest alone or as part of complex phenotypes. In the era of next-generation sequencing (NGS), the list of monogenic complex movement disorders is rapidly growing. This review will explore the main features of these newly identified conditions.
Mutations in ADCY5 and PDE10A have been identified as important causes of childhood-onset dyskinesias and KMT2B mutations as one of the most frequent causes of complex dystonia in children. The delineation of the phenotypic spectrum associated with mutations in ATP1A3, FOXG1, GNAO1, GRIN1, FRRS1L, and TBC1D24 is revealing an expanding genetic overlap between epileptic encephalopathies, developmental delay/intellectual disability, and hyperkinetic movement disorders,. Thanks to NGS, the etiology of several complex hyperkinetic movement disorders has been elucidated. Importantly, NGS is changing the way clinicians diagnose these complex conditions. Shared molecular pathways, involved in early stages of brain development and normal synaptic transmission, underlie basal ganglia dysfunction, epilepsy, and other neurodevelopmental disorders.
运动过度障碍可单独出现或作为复杂表型的一部分。在新一代测序（NGS）时代，越来越多的单基因复杂运动障碍被发现。本文将探讨这些新确定疾病的主要特征。
ADCY5 和 PDE10A 的突变被认为是儿童发病运动障碍的重要原因，而 KMT2B 突变是儿童复杂肌张力障碍最常见的原因之一。ATP1A3、FOXG1、GNAO1、GRIN1、FRRS1L 和 TBC1D24 基因突变相关表型谱的描绘揭示了癫痫性脑病、发育迟缓/智力障碍和运动过度障碍之间遗传重叠的扩大。由于 NGS，几种复杂运动过度障碍的病因已被阐明。重要的是，NGS 正在改变临床医生诊断这些复杂疾病的方式。参与大脑早期发育和正常突触传递的共同分子途径是基底节功能障碍、癫痫和其他神经发育障碍的基础。
