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Diagnostic yield of testing for RFC1 repeat expansions in patients with unexplained adult-onset cerebellar ataxia
  1. Sien Hilde Van Daele1,2,3,
  2. Sascha Vermeer4,
  3. Amélie Van Eesbeeck4,
  4. Laura Lannoo1,
  5. Valérie Race4,
  6. Philip van Damme1,2,3,
  7. Kristl Claeys1,2,
  8. Wim Vandenberghe1,2
  1. 1 Department of Neurology, University Hospitals Leuven, Leuven, Flanders, Belgium
  2. 2 Department of Neurosciences and Leuven Brain Institute, KU Leuven, Leuven, Flanders, Belgium
  3. 3 Center for Brain & Disease Research, VIB, Leuven, Flanders, Belgium
  4. 4 Center for Human Genetics, University Hospitals Leuven, Leuven, Flanders, Belgium
  1. Correspondence to Professor Wim Vandenberghe, Department of Neurology, University Hospitals Leuven, Leuven 3000, Belgium; wim.vandenberghe{at}

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Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is an adult-onset, slowly progressive neurodegenerative disorder characterised in its full form by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Autonomic dysfunction and dry cough are also frequent features. CANVAS is usually sporadic, but occasionally occurs in siblings. Recently, a biallelic intronic AAGGG repeat expansion (AAGGG)exp in RFC1 was identified as the cause in almost all tested familial cases with full CANVAS syndrome.1 2 Interestingly, biallelic (AAGGG)exp in RFC1 were also found in 22% of sporadic, previously idiopathic late-onset ataxia cases.1 The percentage of positive cases increased to 63% if only sporadic patients with combined late-onset cerebellar ataxia and sensory neuropathy were considered, and to 92% in sporadic cases with full CANVAS.1 In a cross-sectional description of 100 patients with biallelic RFC1 (AAGGG)exp, all cases had sensory neuropathy on nerve conduction studies (NCS), while only 79% of cases had cerebellar involvement.3 Whether biallelic RFC1 (AAGGG)exp can cause cerebellar ataxia without sensory neuropathy, remains uncertain. Here, we determined the diagnostic yield of testing for RFC1 repeat expansions in a single-centre cohort of unexplained adult-onset ataxia cases.

Patients and methods

We included all index patients with ataxia who were evaluated at University Hospitals Leuven in the Movement Disorders Clinic between March 2005 and September 2019 or the Neuromuscular Clinic between January 2000 and December 2018 and fulfilled the following criteria: (1) onset age 18 years or older (onset as early as 19 years has been reported in an RFC1 case)3; (2) ataxia as prominent clinical feature; (3) clinical evidence for cerebellar …

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  • Contributors Study concept and design: WV. Acquisition of data: SHVD, LL, WV and AVE. Analysis and interpretation of data: SHVD, SV, AVE and WV. Drafting the manuscript: SHVD and SV. Critical revision of the manuscript for important intellectual content: AVE, LL, VR, PvD, KC and WV.

  • Funding SHVD is funded by a PhD fellowship of the Research Foundation-Flanders (FWO) (1164018N,file number 40900). PvD and WV are Senior Clinical investigators of FWO. PvD is supportedby the ALS Liga België and the KU Leuven funds '“Een Hart voor ALS', 'Laeversfonds voorALS Onderzoek' and the 'Valéry Perrier Race against ALS Fund'.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the institutional Ethics Committee (approval number: S61184).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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