Highlights
- •Pathogenic RFC1 expansions cause a heterogenic disorder beyond CANVAS syndrome.
- •Peripheral nervous system involvement is a hallmark of multisystemic RFC1 disease.
- •RFC1 expansions are a frequent cause of sensory neuropathy of unexplained aetiology.
- •Identification of key features can improve selection criteria for genetic testing.
Abstract
Introduction
Pathogenic expansions in RFC1 have been described as a cause of a spectrum of disorders including late-onset ataxia,
chronic cough, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).
Sensory neuronopathy/neuropathy appears to be a major symptom of RFC1-disorder, and
RFC1 expansions are common in patients with sensory chronic idiopathic axonal neuropathy
or sensory ganglionopathy. We aimed to investigate RFC1 expansions in patients with suspected RFC1-related disease followed-up in a Neuromuscular
Diseases Unit, with a particular interest in the involvement of the peripheral nervous
system.
Methods
We recruited twenty consecutive patients based on the presence of at least two of
the following features: progressive ataxia, sensory neuropathy/neuronopathy, vestibulopathy
and chronic cough. Medical records were retrospectively reviewed for a detailed clinical
description. More extensive phenotyping of the RFC1-positive patients and clinical
comparison between RFC1 positive and negative patients were performed.
Results
Biallelic AAGGG repeat expansions were identified in 13 patients (65%). The most frequent
symptoms were chronic cough and sensory disturbances in the lower extremities (12/13).
Only 4 patients (31%) had complete CANVAS. The phenotypes were sensory ataxia and
sensory symptoms in extremities in 4/13; sensory ataxia, sensory symptoms, and vestibulopathy
in 3/13; sensory symptoms plus chronic cough in 2/13. Chronic cough and isolated sensory
neuronopathy were significantly more prevalent in RFC1-positive patients.
Conclusion
Pathogenic RFC1 expansions are a common cause of sensory neuropathy/neuronopathy and should be considered
in the approach to these patients. Identification of key symptoms or detailed interpretation
of nerve conduction studies may improve patient selection for genetic testing.
Keywords
Abbreviations:
CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome), DRG (dorsal root ganglia), CIAP (chronic idiopathic axonal polyneuropathies), PNS (peripheral nervous system), RFC1 (repat factor complex 1), PCR (polymerase chain reaction), NCS (nerve conduction studies), ANS (autonomic nervous system), SSEPs (somatosensory evoked potentials), CMAP (compound muscle action potential), VEMP (vestibular evoked myogenic potential), CSF (cerebrospinal fluid)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 27, 2023
Accepted:
January 22,
2023
Received in revised form:
January 19,
2023
Received:
June 30,
2022
Footnotes
☆Part of this material is contained within a presentation given at the LXXIII annual meeting of the Spanish Neurology Society, virtual meeting, 24TH November 2021 and at the 2022 Peripheral Nerve Society Annual Meeting, Miami, 14-17th May 2022.
Identification
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© 2023 Published by Elsevier B.V.
