Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion.
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Authors
Cortese, Andrea
Tozza, Stefano
Yau, Wai Yan
Rossi, Salvatore
Beecroft, Sarah J
Jaunmuktane, Zane
Dyer, Zoe
Ravenscroft, Gianina
Lamont, Phillipa J
Mossman, Stuart
Chancellor, Andrew
Maisonobe, Thierry
Pereon, Yann
Cauquil, Cecile
Colnaghi, Silvia
Mallucci, Giulia
Curro, Riccardo
Tomaselli, Pedro J
Thomas-Black, Gilbert
Sullivan, Roisin
Efthymiou, Stephanie
Rossor, Alexander M
Laurá, Matilde
Pipis, Menelaos
Horga, Alejandro
Polke, James
Kaski, Diego
Marques, Wilson
Tassorelli, Cristina
Devigili, Grazia
Leonardis, Lea
Wood, Nick W
Bronstein, Adolfo
Giunti, Paola
Züchner, Stephan
Stojkovic, Tanya
Laing, Nigel
Roxburgh, Richard H
Houlden, Henry
Reilly, Mary M
Publication Date
2020-02-01Journal Title
Brain
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Volume
143
Issue
2
Pages
480-490
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
Cortese, A., Tozza, S., Yau, W. Y., Rossi, S., Beecroft, S. J., Jaunmuktane, Z., Dyer, Z., et al. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion.. Brain, 143 (2), 480-490. https://doi.org/10.1093/brain/awz418
Abstract
Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major cause of late onset ataxia. Here we describe the full spectrum of the disease phenotype in our first 100 genetically confirmed carriers of biallelic repeat expansions in RFC1 and identify the sensory neuropathy as a common feature in all cases to date. All patients were Caucasian and half were sporadic. Patients typically reported progressive unsteadiness starting in the sixth decade. A dry spasmodic cough was also frequently associated and often preceded by decades the onset of walking difficulty. Sensory symptoms, oscillopsia, dysautonomia and dysarthria were also variably associated. The disease seems to follow a pattern of spatial progression from the early involvement of sensory neurons, to the later appearance of vestibular and cerebellar dysfunction. Half of the patients needed walking aids after 10 years of disease duration and a quarter were wheelchair dependent after 15 years. Overall, two-thirds of cases had full CANVAS. Sensory neuropathy was the only manifestation in 15 patients. Sixteen patients additionally showed cerebellar involvement, and six showed vestibular involvement. The disease is very likely to be underdiagnosed. Repeat expansion in RFC1 should be considered in all cases of sensory ataxic neuropathy, particularly, but not only, if cerebellar dysfunction, vestibular involvement and cough coexist.
Keywords
Cerebellum, Humans, Vestibular Neuronitis, Ataxia, Cerebellar Ataxia, Reflex, Abnormal, Sensation Disorders, Peripheral Nervous System Diseases, Syndrome, Neurologic Examination, Aged, Aged, 80 and over, Middle Aged, Female, Male
Sponsorship
Wellcome Trust (212219/Z/18/Z)
Medical Research Council (MR/N025431/2)
Wellcome Trust (109915_A_15_Z)
Identifiers
External DOI: https://doi.org/10.1093/brain/awz418
This record's URL: https://www.repository.cam.ac.uk/handle/1810/304589
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