Acute Vestibular Syndrome Unmasking an RFC1-Spectrum Disorder

Neurol Genet. 2025 Jan 16;11(1):e200238. doi: 10.1212/NXG.0000000000200238. eCollection 2025 Feb.

Abstract

Objectives: Since the discovery of biallelic pentanucleotide expansions in RFC1 as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome, a wide and growing clinical spectrum has emerged. In this article, we report a man with acute vestibular syndrome that likely unmasked a RFC1-spectrum disorder.

Methods: Detailed clinical evaluation, neuroimaging, nerve conduction studies, evaluation of vestibular function, and short-read whole-genome sequencing and targeted long-read adaptive sequencing were performed.

Results: Clinical follow-up after acute vestibular syndrome revealed bilateral vestibular areflexia and a gait abnormality with the Scale for the Assessment and Rating of Ataxia score of 5. Brain MRI was normal while 2 electroneurography tests did not show neuropathy. However, severe cough spells raised the suspicion of a RFC1-spectrum disorder. WGS screening detected a recessive intronic pentanucleotide expansion in RFC1, which was verified and sized using long-read adaptive sequencing.

Discussion: This is an unusual presentation; oscillopsia after an acute vestibular syndrome and cough spells should alert clinicians about a RFC1-spectrum disorder, even in the absence of neuropathy and neuroradiologic abnormalities.