Department of Pediatric Neurology, IRCCS Foundation Carlo Besta Neurological Institute, Via Celoria 11, 20131 Milan, Italy; Molecular Neurogenetics Unit, IRCCS Foundation Carlo Besta Neurological Institute, Via L. Temolo 4, 20126 Milan, Italy; Department of Medicine and Surgery, PhD Programme in Molecular and Translational Medicine, Milan Bicocca University, Via Cadore 48, 20900 Monza, Italy.
Department of Pediatric Neurology, IRCCS Foundation Carlo Besta Neurological Institute, Via Celoria 11, 20131 Milan, Italy.
Eur J Paediatr Neurol. 2018 Mar;22(2):257-263. doi: 10.1016/j.ejpn.2017.12.009. Epub 2017 Dec 21.
Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) are three distinct, yet partially overlapping clinical syndromes that have long been thought to be allelic disorders. From 2004 to 2012, both autosomal dominant and de novo mutations in ATP1A3 have been detected in patients affected by these three conditions. Growing evidence suggests that AHC, RDP and CAPOS syndrome are part of a large and continuously expanding clinical spectrum and share some recurrent clinical features, such as abrupt-onset, asymmetric anatomical distribution and the presence of triggering factors, which are highly suggestive of ATP1A3 mutations. In this review, we will highlight the main clinical and genetic features of ATP1A3-related disorders focussing on shared and distinct features that can be helpful in clinical practice to individuate mutation carriers.
儿童交替性偏瘫（AHC）、快速进展性肌张力障碍帕金森病（RDP）和 CAPOS 综合征（小脑共济失调、反射消失、高弓足、视神经萎缩和感觉神经性听力损失）是三种不同但部分重叠的临床综合征，长期以来一直被认为是等位基因疾病。从 2004 年到 2012 年，这些病症的患者中检测到了常染色体显性和从头突变的 ATP1A3。越来越多的证据表明，AHC、RDP 和 CAPOS 综合征是一个大型且不断扩展的临床谱的一部分，具有一些反复出现的临床特征，如突发性、非对称解剖分布和存在触发因素，这强烈提示存在 ATP1A3 突变。在这篇综述中，我们将重点介绍与 ATP1A3 相关疾病的主要临床和遗传特征，强调在临床实践中有助于确定突变携带者的共同和独特特征。
