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Background <p>Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic repeat expansions in the <i>RFC1</i> gene. Chronic cough can precede the neurological features of CANVAS by decades and, in some instances, may be the sole clinical manifestation. However, the prevalence of biallelic <i>RFC1</i> repeat expansions among patients with unexplained chronic cough (UCC), as well as the diagnostic utility of targeted neurological screening in this setting, remains unclear.</p> Methods <p>In this 6-month pilot study, 13 consecutive patients with UCC underwent a standardized neurological evaluation and screening nerve conduction studies (NCS) during a single clinical visit. All patients were subsequently tested for <i>RFC1</i> repeat expansions. Those carrying biallelic pathogenic expansions (RFC1+) were further assessed with extended NCS, electrochemical skin conductance (ESC), and thermal quantitative sensory testing (QST).</p> Results <p>Three patients (23%) were RFC1+. Clinical and demographic features did not significantly differ between RFC1+ and RFC1– groups. All RFC1+ individuals exhibited marked bilateral reduction in radial and sural sensory nerve action potential (SNAP) amplitudes. In contrast, only two RFC1– patients showed reduced sural SNAPs. QST revealed impaired cold detection thresholds with preserved warm detection in all RFC1+ cases, while ESC results were normal.</p> Conclusions <p>These findings suggest that standardized neurological and electrophysiological assessment can detect subclinical sensory neuropathy in UCC patients lacking overt neurological symptoms, thereby identifying those more likely to carry <i>RFC1</i> expansions. The observed 23% prevalence supports incorporating <i>RFC1</i> testing into the diagnostic approach for selected UCC patients, particularly when radial SNAP amplitudes are reduced.</p>

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Targeted neurological screening for RFC1-related disease in unexplained chronic cough

  • 期刊论文

  • 发表日期：

    2026年3月16日

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  • Vicente Gajate-García,
  • María Fenollar-Cortés,
  • Juan Luis Rodríguez-Hermosa,
  • Marina Lara-González,
  • Clara Herrero-Forte,
  • Iván Muerte-Moreno,
  • Miriam Calle-Rubio,
  • Alejandro Horga

摘要

Background

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic repeat expansions in the RFC1 gene. Chronic cough can precede the neurological features of CANVAS by decades and, in some instances, may be the sole clinical manifestation. However, the prevalence of biallelic RFC1 repeat expansions among patients with unexplained chronic cough (UCC), as well as the diagnostic utility of targeted neurological screening in this setting, remains unclear.

Methods

In this 6-month pilot study, 13 consecutive patients with UCC underwent a standardized neurological evaluation and screening nerve conduction studies (NCS) during a single clinical visit. All patients were subsequently tested for RFC1 repeat expansions. Those carrying biallelic pathogenic expansions (RFC1+) were further assessed with extended NCS, electrochemical skin conductance (ESC), and thermal quantitative sensory testing (QST).

Results

Three patients (23%) were RFC1+. Clinical and demographic features did not significantly differ between RFC1+ and RFC1– groups. All RFC1+ individuals exhibited marked bilateral reduction in radial and sural sensory nerve action potential (SNAP) amplitudes. In contrast, only two RFC1– patients showed reduced sural SNAPs. QST revealed impaired cold detection thresholds with preserved warm detection in all RFC1+ cases, while ESC results were normal.

Conclusions

These findings suggest that standardized neurological and electrophysiological assessment can detect subclinical sensory neuropathy in UCC patients lacking overt neurological symptoms, thereby identifying those more likely to carry RFC1 expansions. The observed 23% prevalence supports incorporating RFC1 testing into the diagnostic approach for selected UCC patients, particularly when radial SNAP amplitudes are reduced.