Phenotypic variability in cerebellar ataxia, neuropathy, vestibular areflexia syndrome, CANVAS: a single centre case series

<h3>Background</h3> Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described clinical entity with autosomal recessive inheritance and typical onset in late-middle age. CANVAS patients classically display a triad of cerebellar, sensory and vestibular dysfunction, and neurophysiology typically demonstrates dorsal root ganglionopathy (DRG). Biallelic pentanucleotide AAGGG repeat expansions are present in the large majority of sporadic and familial cases, and increased testing has led to an expanding phenotype. Formes frustes, chronic cough, and retained or brisk tendon reflexes are recognised. <h3>Methods</h3> We performed a retrospective analysis of the demographics, clinical features and investigations of a tertiary neurosciences centre cohort with confirmed biallelic RFC1 expansion. We explore clinical findings in line with previously presented cohorts, highlighting phenotypic variability within the cohort.. <h3>Results</h3> We identified 49 patients (57%F) with biallelic RFC1 expansions and electrophysiological evidence of DRG. Age at presentation was 61 years. 9 individuals had affected family members. Neuropathic pain was prevalent (57%) as was chronic cough (59%), including cough syncope in 2 patients. Atypical electrophysiological findings were seen in 6 patients with demyelinating (n=3), fasciculations (n=1), sensorimotor (n=1) and FOSMN-like (n=1) patterns. <h3>Conclusions</h3> Phenotypic variability is increasingly recognised in CANVAS and should inform clinical practice in RFC1 testing.