RFC1-associated disease with an atypical parkinsonism syndrome phenotype

In 2019, it was established that biallelic expansion of pentanucleotide AAGGG repeats in intron 2 of the RFC1 gene is the cause of CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome). In addition to the classic triad of symptoms (cerebellar ataxia, sensory neuropathy, vestibular areflexia), the condition may be accompanied by extrapyramidal and autonomic disturbances, which complicates the differential diagnosis with atypical forms of parkinsonism. This article presents the clinical case of a 69-year-old patient with biallelic RFC1 expansion, whose clinical presentation was dominated by asymmetric parkinsonism, sensory-cerebellar ataxia and autonomic dysfunction. Instrumental studies revealed sensory axonal polyneuropathy, bilateral vestibulopathy and oculomotor disturbances characteristic of cerebellar involvement. Multiple system atrophy and corticobasal degeneration were considered in the differential diagnosis. The combination of sensory neuropathy, cerebellar ataxia and vestibular areflexia formed the basis for molecular genetic testing, which confirmed a biallelic RFC1 expansion. This case highlights the multisystem nature of RFC1-associated disorders and demonstrates that parkinsonism and early autonomic dysfunction may form part of the clinical spectrum of this condition. The findings also raise the possibility of RFC1-associated disease co-occurring with neurodegenerative processes from the group of α-synucleinopathies.