CANVAS: case report on a novel repeat expansion disorder with late-onset ataxia

This article presents the case of a 74-year-old female patient who first developed a progressive disease with sensory neuropathy, cerebellar ataxia and bilateral vestibulopathy at the age of 60 years. The family history was unremarkable. Magnetic resonance imaging (MRI) showed atrophy of the cerebellum predominantly in the vermis and atrophy of the spinal cord. The patient was given the syndromic diagnosis of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In 2019 the underlying genetic cause of CANVAS was discovered to be an intronic repeat expansion in the RFC1 gene with autosomal recessive inheritance. The patient exhibited the full clinical picture of CANVAS and was tested positive for this repeat expansion on both alleles. The CANVAS is a relatively frequent cause of late-onset hereditary ataxia (estimated prevalence 5‑13/100,000). In contrast to the present patient, the full clinical picture is not always present. Therefore, testing for the RFC1 gene expansion is recommended in the work-up of patients with otherwise unexplained late-onset sporadic ataxia. As intronic repeat expansions cannot be identified by next generation sequencing methods, specific testing is necessary

CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions

The ataxias are a group of disorders that manifest with balance, movement, speech and visual problems. They can arise due to dysfunction of the cerebellum, the vestibular system and/or the sensory neurons. Genetic defects are a common cause of chronic ataxia, particularly common are repeat expansions in this group of conditions. Co-occurrence of cerebellar ataxia with neuropathy and vestibular areflexia syndrome has been termed CANVAS. Although CANVAS is a rare syndrome, on discovery of biallelic expansions in the second intron of replication factor C subunit 1 (RFC1) gene, we and others have found the phenotype is broad and RFC1 expansions are a common cause of late-onset progressive ataxia. We aim to provide a review and update on recent developments in CANVAS and populations, where the disorder has been reported. We have also optimised a protocol for RFC1 expansion screening which is described herein and expanded phenotype after analysing late-onset ataxia patients from around the world

CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions

The ataxias are a group of disorders that manifest with balance, movement, speech and visual problems. They can arise due to dysfunction of the cerebellum, the vestibular system and/or the sensory neurons. Genetic defects are a common cause of chronic ataxia, particularly common are repeat expansions in this group of conditions. Co-occurrence of cerebellar ataxia with neuropathy and vestibular areflexia syndrome has been termed CANVAS. Although CANVAS is a rare syndrome, on discovery of biallelic expansions in the second intron of replication factor C subunit 1 (RFC1) gene, we and others have found the phenotype is broad and RFC1 expansions are a common cause of late-onset progressive ataxia.We aim to provide a review and update on recent developments in CANVAS and populations, where the disorder has been reported. We have also optimised a protocol for RFC1 expansion screening which is described herein and expanded phenotype after analysing late-onset ataxia patients from around the world

CANVAS: case report on a novel repeat expansion disorder with late-onset ataxia

This article presents the case of a 74-year-old female patient who first developed a progressive disease with sensory neuropathy, cerebellar ataxia and bilateral vestibulopathy at the age of 60 years. The family history was unremarkable. Magnetic resonance imaging (MRI) showed atrophy of the cerebellum predominantly in the vermis and atrophy of the spinal cord. The patient was given the syndromic diagnosis of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In 2019 the underlying genetic cause of CANVAS was discovered to be an intronic repeat expansion in the RFC1 gene with autosomal recessive inheritance. The patient exhibited the full clinical picture of CANVAS and was tested positive for this repeat expansion on both alleles. The CANVAS is a relatively frequent cause of late-onset hereditary ataxia (estimated prevalence 5‑13/100,000). In contrast to the present patient, the full clinical picture is not always present. Therefore, testing for the RFC1 gene expansion is recommended in the work-up of patients with otherwise unexplained late-onset sporadic ataxia. As intronic repeat expansions cannot be identified by next generation sequencing methods, specific testing is necessary