PT - JOURNAL ARTICLE AU - Andrea Cortese AU - Riccardo Curro' AU - Elisa Vegezzi AU - Wai Yan Yau AU - Henry Houlden AU - Mary M Reilly TI - Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects AID - 10.1136/practneurol-2020-002822 DP - 2022 Feb 01 TA - Practical Neurology PG - 14--18 VI - 22 IP - 1 4099 - http://pn.bmj.com/content/22/1/14.short 4100 - http://pn.bmj.com/content/22/1/14.full SO - Pract Neurol2022 Feb 01; 22 AB - Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) typically presents in middle life with a combination of neuropathy, ataxia and vestibular disease, with patients reporting progressive imbalance, oscillopsia, sensory disturbance and a dry cough. Examination identifies a sensory neuropathy or neuronopathy and bilaterally impaired vestibulo-ocular reflex. The underlying genetic basis is of biallelic AAGGG expansions in the second intron of replication factor complex subunit 1 (RFC1). The frequency and phenotype spectrum of RFC1 disease is expanding, ranging from typical CANVAS to site-restricted variants affecting the sensory nerves, cerebellum and/or the vestibular system. Given the wide phenotype spectrum of RFC1, the differential diagnosis is broad. RFC1 disease due to biallelic AAGGG expansions is probably the most common cause of recessive ataxia. The key to suspecting the disease (and prompt genetic testing) is a thorough clinical examination assessing the three affected systems and noting the presence of chronic cough.