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dc.contributor.authorCortese, Andrea
dc.contributor.authorTozza, Stefano
dc.contributor.authorYau, Wai Yan
dc.contributor.authorRossi, Salvatore
dc.contributor.authorBeecroft, Sarah J
dc.contributor.authorJaunmuktane, Zane
dc.contributor.authorDyer, Zoe
dc.contributor.authorRavenscroft, Gianina
dc.contributor.authorLamont, Phillipa J
dc.contributor.authorMossman, Stuart
dc.contributor.authorChancellor, Andrew
dc.contributor.authorMaisonobe, Thierry
dc.contributor.authorPereon, Yann
dc.contributor.authorCauquil, Cecile
dc.contributor.authorColnaghi, Silvia
dc.contributor.authorMallucci, Giulia
dc.contributor.authorCurro, Riccardo
dc.contributor.authorTomaselli, Pedro J
dc.contributor.authorThomas-Black, Gilbert
dc.contributor.authorSullivan, Roisin
dc.contributor.authorEfthymiou, Stephanie
dc.contributor.authorRossor, Alexander M
dc.contributor.authorLaurá, Matilde
dc.contributor.authorPipis, Menelaos
dc.contributor.authorHorga, Alejandro
dc.contributor.authorPolke, James
dc.contributor.authorKaski, Diego
dc.contributor.authorHorvath, Rita
dc.contributor.authorChinnery, Patrick F
dc.contributor.authorMarques, Wilson
dc.contributor.authorTassorelli, Cristina
dc.contributor.authorDevigili, Grazia
dc.contributor.authorLeonardis, Lea
dc.contributor.authorWood, Nick W
dc.contributor.authorBronstein, Adolfo
dc.contributor.authorGiunti, Paola
dc.contributor.authorZüchner, Stephan
dc.contributor.authorStojkovic, Tanya
dc.contributor.authorLaing, Nigel
dc.contributor.authorRoxburgh, Richard H
dc.contributor.authorHoulden, Henry
dc.contributor.authorReilly, Mary M
dc.date.accessioned2020-04-21T23:30:21Z
dc.date.available2020-04-21T23:30:21Z
dc.date.issued2020-02-01
dc.identifier.issn0006-8950
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/304589
dc.description.abstractAtaxia, 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.
dc.format.mediumPrint
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCerebellum
dc.subjectHumans
dc.subjectVestibular Neuronitis
dc.subjectAtaxia
dc.subjectCerebellar Ataxia
dc.subjectReflex, Abnormal
dc.subjectSensation Disorders
dc.subjectPeripheral Nervous System Diseases
dc.subjectSyndrome
dc.subjectNeurologic Examination
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.titleCerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion.
dc.typeArticle
prism.endingPage490
prism.issueIdentifier2
prism.publicationDate2020
prism.publicationNameBrain
prism.startingPage480
prism.volume143
dc.identifier.doi10.17863/CAM.51671
dcterms.dateAccepted2019-11-27
rioxxterms.versionofrecord10.1093/brain/awz418
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-02
dc.contributor.orcidHorvath, Rita [0000-0002-9841-170X]
dc.contributor.orcidChinnery, Patrick [0000-0002-7065-6617]
dc.identifier.eissn1460-2156
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (212219/Z/18/Z)
pubs.funder-project-idMedical Research Council (MR/N025431/2)
pubs.funder-project-idWellcome Trust (109915_A_15_Z)
cam.issuedOnline2020-02-10


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International