Department of Neuromuscular Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
J Neurol. 2021 Mar;268(3):1119-1126. doi: 10.1007/s00415-020-10183-0. Epub 2020 Sep 10.
The ataxias are a group of disorders that manifest with balance, movement, speech and visual problems. They can arise due to dysfunction of the cerebellum, the vestibular system and/or the sensory neurons. Genetic defects are a common cause of chronic ataxia, particularly common are repeat expansions in this group of conditions. Co-occurrence of cerebellar ataxia with neuropathy and vestibular areflexia syndrome has been termed CANVAS. Although CANVAS is a rare syndrome, on discovery of biallelic expansions in the second intron of replication factor C subunit 1 (RFC1) gene, we and others have found the phenotype is broad and RFC1 expansions are a common cause of late-onset progressive ataxia.We aim to provide a review and update on recent developments in CANVAS and populations, where the disorder has been reported. We have also optimised a protocol for RFC1 expansion screening which is described herein and expanded phenotype after analysing late-onset ataxia patients from around the world.
共济失调是一组以平衡、运动、言语和视觉问题为表现的疾病。它们可能由于小脑、前庭系统和/或感觉神经元的功能障碍而发生。遗传缺陷是慢性共济失调的常见原因，在这一组疾病中，重复扩展尤为常见。小脑共济失调伴多发性神经病和前庭反射消失综合征的同时发生被称为 CANVAS。虽然 CANVAS 是一种罕见的综合征，但在发现复制因子 C 亚基 1（RFC1）基因第二内含子中的双等位基因扩展后，我们和其他人发现表型广泛，RFC1 扩展是迟发性进行性共济失调的常见原因。我们旨在提供关于 CANVAS 和已报道该疾病人群的最新研究进展综述。我们还优化了 RFC1 扩展筛查方案，并在对来自世界各地的迟发性共济失调患者进行分析后扩展了表型。
