Bilateral vestibulopathy in RFC1-positive CANVAS is distinctly different compared to FGF14-linked spinocerebellar ataxia 27B

The recent discoveries of two new repeat expansion disorders for late-onset cerebellar ataxia (CA), frequently accompanied by vestibulopathy and neuropathy, shed new light on ataxia research. Biallelic intronic repeat expansions in the RFC1 (replication factor C subunit) gene [1, 2] are disease causing in about 90% of Cerebellar ataxia, Neuropathy, and Vestibular Areflexia Syndrome (CANVAS) patients [3, 4], while heterozygous intronic repeat expansions in the Fibro-blast Growth Factor 14 ( FGF14 ) gene explain a relevant number of late-onset CA cases [5–7]. Bilateral vestibulopa-thy (BV) is a characteristic feature of the CANVAS phenotype of RFC1-linked disease, and emerging data suggest that FGF14 repeat expansion carriers may also exhibit vestibular hypofunction [5, 6, 8]. However, differences in the severity of BV, potentially allowing conclusions about the underlying etiology, are yet to be compared between FGF14 and RFC1 repeat expansion carriers. Here, we investigated the role of BV in the differential diagnosis between RFC1-, FGF14-expansion - positive, and repeat-expansion-negative