CLINICAL CHARACTERISTICS: The phenotypic spectrum of RFC1 -related disorders ranges from c erebellar a taxia, n europathy, v estibular a reflexia s yndrome (CANVAS) to phenotypes that involve predominantly or exclusively the peripheral sensory nerves with or without vestibular and cerebellar involvement. Onset is in adulthood (range: age 25-80 years)....
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Discussion
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Audiologists should be aware that unexplained sensorineural hearing loss combined with vestibular dysfunction may point to RFC1-related disorder; refer patients with this presentation for genetic evaluation, but no change to routine audiological treatment protocols is indicated at this time.
RFC1-related disorders represent an underdiagnosed genetic cause of combined sensorineural hearing loss and vestibular dysfunction, and recognition of the full phenotypic spectrum can improve diagnostic yield for audiologists encountering unexplained audiovestibular presentations.
- 01RFC1-related disorders are caused by biallelic repeat expansions in the RFC1 gene.
- 02Core features include cerebellar ataxia, sensory neuropathy, and vestibular areflexia (CANVAS syndrome).
- 03Sensorineural hearing loss and vestibular dysfunction are prominent auditory/vestibular manifestations.
- 04GeneReviews provides a curated, expert-authored summary of the phenotypic spectrum and management guidance.
- 05Genetic testing is required for definitive diagnosis; audiological findings alone are not diagnostic.
RFC1-related disorders include vestibular and sensorineural auditory features as part of their phenotypic spectrum.
guidelinesupportedRFC1 biallelic repeat expansions are a genetic cause of CANVAS syndrome (cerebellar ataxia, neuropathy, vestibular areflexia syndrome).
guidelinesupported- PMID
- 33237689
- Journal
- GeneReviews (NCBI Bookshelf / University of Washington)
- Publication type
- review
- Evidence level
- 5
- Population
- Individuals with RFC1-related disorders presenting with cerebellar ataxia, sensory neuropathy, vestibular dysfunction, and/or sensorineural hearing loss
- Intervention
- Characterisation of the phenotypic spectrum of RFC1-related disorders
Primary outcomes
Description of clinical features including vestibular and sensorineural auditory manifestations; Genotype–phenotype correlations for RFC1 biallelic repeat expansions; Diagnostic and management recommendations