Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (canvas): an important cause of late-onset ataxia with unique clinical features

Acta Neurol Belg. 2022 Aug;122(4):939-945. doi: 10.1007/s13760-021-01721-2. Epub 2021 Jun 8.

Abstract

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Recently, a biallelic intronic AAGGG repeat expansion, (AAGGG)exp, in the Replication Factor C1 (RFC1) gene was identified as the cause of this disorder. In this study, we describe the phenotypic features of five patients from five different families diagnosed as CANVAS. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. Our study describes clinical findings, histopathological features and diagnostic clues of CANVAS from Turkey, a country with a high consanguineous marriage rate. Repeat expansion in the RFC1 gene should be considered in all cases with late-onset ataxia, especially when sensory disturbances, vestibular involvement and persistent coughing coexist.

Keywords: Coughing; Diagnosis; Genetic; Polyneuropathy; RFC1.

MeSH terms

  • Adult
  • Ataxia / complications
  • Bilateral Vestibulopathy* / complications
  • Bilateral Vestibulopathy* / diagnosis
  • Bilateral Vestibulopathy* / genetics
  • Cerebellar Ataxia* / complications
  • Cerebellar Ataxia* / genetics
  • Gait Ataxia
  • Humans
  • Middle Aged
  • Peripheral Nervous System Diseases* / complications
  • Sensation Disorders / complications
  • Syndrome
  • Vestibular Diseases* / etiology