Expanding the Clinical Spectrum of RFC1 Gene Mutations

Abstract

Biallelic intronic repeat expansion in the replication factor complex unit 1 (RFC1) gene has recently been described as a cause of late onset ataxia with degeneration of the cerebellum, sensory pathways and the vestibular apparatus. This condition is termed cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Since the identification of this novel gene mutation, the phenotypic spectrum of RFC1 mutations continues to expand and includes not only CANVAS but also slowly progressive cerebellar ataxia, ataxia with chronic cough (ACC), isolated sensory neuropathy and multisystemic diseases. We present a patient with a genetically confirmed intronic repeat expansion in the RFC1 gene with a symptom complex not described previously.

Keywords: Ataxia; CANVAS; RFC1.

Figure 1.

Pedigree of the affected family. There was no similar illness in the family.

Figure 2.

Brain magnetic resonance imaging of the patient with a RFC1 gene mutation. T2WI (A and B) shows relatively preserved cerebellar hemispheres with prominent vermian atrophy. Sagittal (C) and parasagittal (D) FLAIR sequences show classical atrophy restricted to lobules VI, VIIA and VIIB of the cerebellum. T2WI, T2 weighted image; FLAIR, fluid-attenuated inversion recovery.