Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFCI repeat expansion

被引：163

作者：

Cortese, Andrea ^{[1
,2
,3
]}

Tozza, Stefano ^{[1
,2
,4
]}

Yau, Wai Yan ^{[1
,2
]}

Rossi, Salvatore ^{[1
,2
,5
,6
]}

Beecroft, Sarah J. ^{[7
]}

Jaunmuktane, Zane ^{[2
,8
]}

Dyer, Zoe ^{[9
,10
]}

Ravenscroft, Gianina ^{[7
]}

Lamont, Phillipa J. ^{[11
]}

Mossman, Stuart ^{[12
]}

Chancellor, Andrew ^{[13
]}

Maisonobe, Thierry ^{[14
]}

Pereon, Yann ^{[15
]}

Cauquil, Cecile ^{[16
]}

Colnaghi, Silvia ^{[17
]}

Mallucci, Giulia ^{[17
]}

Curro, Riccardo ^{[3
]}

Tomaselli, Pedro J. ^{[18
]}

Thomas-Black, Gilbert ^{[2
,8
]}

Sullivan, Roisin ^{[1
,2
]}

Efthymiou, Stephanie ^{[1
,2
]}

Rossor, Alexander M. ^{[1
,2
]}

Laura, Matilde ^{[1
,2
]}

Pipis, Menelaos ^{[1
,2
]}

Horga, Alejandro ^{[1
,2
]}

Polke, James ^{[1
,2
]}

Kaski, Diego ^{[2
,8
]}

Horvath, Rita ^{[19
]}

Chinnery, Patrick F. ^{[19
,20
]}

Marques, Wilson ^{[18
]}

Tassorelli, Cristina ^{[3
,17
]}

Devigili, Grazia ^{[21
]}

Leonardis, Lea ^{[22
]}

Wood, Nick W. ^{[1
,2
]}

Bronstein, Adolfo ^{[2
,8
]}

Giunti, Paola ^{[2
,8
]}

Zuchner, Stephan ^{[23
,24
]}

Stojkovic, Tanya ^{[25
]}

Laing, Nigel ^{[7
,26
]}

Roxburgh, Richard H. ^{[9
,10
]}

Houlden, Henry ^{[1
,2
]}

Reilly, Mary M. ^{[1
,2
]}

机构：

[1] UCL Queen Sq Inst Neurol, Dept Neuromuscular Dis, London, England

[2] Natl Hosp Neurol, London, England

[3] Univ Pavia, Dept Brain & Behav Sci, Pavia, Italy

[4] Univ Naples Federico II, Dept Neurosci Reprod Sci & Odontostomatol, Naples, Italy

[5] Fdn Policlin Univ A Gemelli IRCSS, Dept Neurol, Rome, Italy

[6] Univ Cattolica Sacro Cuore, Inst Neurol, Rome, Italy

[7] Univ Western Australia, Harry Perkins Inst Med Res, QEII Med Ctr, Ctr Med Res, Nedlands, WA 6009, Australia

[8] UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England

[9] ADHB, Auckland, New Zealand

[10] Univ Auckland, Ctr Brain Res, Neurogenet Res Clin, Auckland, New Zealand

[11] Royal Perth Hosp, Neurogenet Unit, Perth, WA, Australia

[12] Wellington Hosp, Dept Neurol, Wellington 6021, New Zealand

[13] Tauranga Hosp, Dept Neurol, Cameron Rd, Tauranga 3171, New Zealand

[14] Sorbonne Univ prime, Hop Pitie Salpetrie, AP HP, Dept Neurophysiol, Paris, France

[15] CHU Nantes, Hotel Dieu, Reference Ctr Neuromuscular Dis, Nantes, France

[16] CHU Bicetre, AP HP, Dept Neurol, Le Kremlin Bicetre, France

[17] IRCCS Mondino Fdn, Pavia, Italy

[18] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Neurol, Ribeirao Preto, Brazil

[19] Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge, England

[20] Univ Cambridge, MRC Mitochondrial Biol Unit, Cambridge, England

[21] Fdn IRCCS Ist Neurol Carlo Besta, UO Neurol 1, Milan, Italy

[22] Univ Med Ctr Ljubljana, Inst Clin Neurophysiol, Div Neurol, Ljubljana, Slovenia

[23] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USA

[24] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA

[25] Sorbonne Univ, Hop Pitie Salpetriere, AP HP, INSERM,UMR S 974,Ctr Reference Malad Neuromuscula, Paris, France

[26] QEII Med Ctr, PathWest Lab Med, Dept Diagnost Genom, Neurogenet Unit, Nedlands, WA, Australia

来源：

BRAIN | 2020年 / 143卷

基金：

英国医学研究理事会; 英国惠康基金; 欧洲研究理事会;

关键词：

sensory neuropathy; cerebellar ataxia; neuropathy; vestibular areflexia syndrome (CANVAS); chronic cough; RFC1; repeat expansion; DIAGNOSTIC-CRITERIA; BILATERAL VESTIBULOPATHY; SURAL NERVE; CANVAS;

D O I：

10.1093/brain/awz418

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：480 / 490

页数：11

共 27 条

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