Chronic cough is common, and in many cases unexplained or refractory to otherwise effective treatment of associated medical conditions. Cough hypersensitivity has developed as a paradigm that helps to explain clinical and research observations that frequently point towards chronic cough as a neuropathic disorder. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described neurological condition whose clinical features include gait ataxia, unsteadiness, peripheral neuropathy, and autonomic dysfunction. Chronic cough is also a common feature of the syndrome, with features of hypersensitivity, often preceding core neurological symptoms by up to 30 years or more. The genetic basis in a majority of cases of CANVAS appears to be biallelic variable repeat intron expansion sequences within RFC1, a gene normally involved in the regulation of DNA replication and repair. The same polymorphism has now been identified at an increased frequency in patients with unexplained or refractory chronic cough in the absence of defining clinical features of CANVAS. This review expands on these points, aiming to increase the awareness of CANVAS amongst clinicians and researchers working with chronic cough. We discuss the implications of a link between RFC1 disease and cough. Improved understanding of CANVAS may lead to an enhanced grasp of the pathophysiology of chronic cough, and new approaches to antitussive treatments.

慢性咳嗽很常见，并且在许多情况下无法解释或无法有效治疗相关疾病。咳嗽过敏症已发展成为一种范例，有助于解释临床和研究观察结果，这些观察结果经常表明慢性咳嗽是一种神经性疾病。小脑共济失调伴神经病变和前庭反射消失综合征 (CANVAS) 是最近描述的一种神经系统疾病，其临床特征包括步态共济失调、不稳定、周围神经病变和自主神经功能障碍。慢性咳嗽也是该综合征的一个常见特征，具有超敏反应的特征，通常在核心神经系统症状出现之前长达 30 年或更长时间。大多数 CANVAS 病例的遗传基础似乎是RFC1内的双等位基因可变重复内含子扩展序列，RFC1 是一种通常参与 DNA 复制和修复调节的基因。在缺乏 CANVAS 临床特征的情况下，在不明原因或难治性慢性咳嗽的患者中，同样的多态性被发现的频率有所增加。本综述对这些要点进行了扩展，旨在提高从事慢性咳嗽工作的临床医生和研究人员对 CANVAS 的认识。我们讨论RFC1疾病与咳嗽之间联系的影响。提高对 CANVAS 的了解可能会增强对慢性咳嗽的病理生理学的掌握，并带来镇咳治疗的新方法。