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Background <p><i>RFC1</i>-related CANVAS and <i>FGF14</i>-related SCA27B are recently recognized genetic causes of late-onset cerebellar ataxia (LOCA). Despite advances in genetic testing, most panels do not detect these intronic repeat expansions, often resulting in repeated testing, delayed diagnosis, and greater patient burden. Vestibular dysfunction is common in both disorders and may help differentiate them from idiopathic LOCA (ILOCA) subtypes, guiding targeted genetic testing.</p> Objectives <p>To evaluate whether vestibulo-ocular reflex (VOR) gain measured by video head impulse test (vHIT) can differentiate CANVAS and SCA27B from ILOCA.</p> Methods <p>We reviewed 290 records of individuals with suspected cerebellar ataxia at the Johns Hopkins Ataxia Center (2023–2025). VOR gains were assessed using vHIT and compared across groups. Diagnostic thresholds were determined using receiver operating characteristic curves, with significance set at <i>p</i> &lt; 0.05.</p> Results <p>Fifth-nine participants were included: 10 CANVAS, 33 SCA27B, and 16 ILOCA, and matched with 31 controls. Bilateral vestibulopathy (VOR gain &lt; 0.6) was present in 80% of CANVAS, 18% of SCA27B, and none of ILOCA (<i>p</i> = 0.024). Mean horizontal VOR gains were significantly lower in CANVAS (0.22) and SCA27B (0.85) than in ILOCA (1.11; <i>p</i> &lt; 0.001). VOR gains &lt; 0.70 differentiated CANVAS/SCA27B from ILOCA (100% specificity, 44% sensitivity), while a threshold of 0.50 distinguished CANVAS from SCA27B (91% specificity and 70% sensitivity).</p> Discussion <p>Reduced VOR gains were common in both CANVAS and SCA27B, and not observed in ILOCA. vHIT metrics may assist in distinguishing these genetic ataxias from ILOCA and each other, supporting potential utility as physiologic biomarkers and guiding targeted genetic testing.</p>

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Video head impulse test differentiates RFC1-CANVAS, FGF14-SCA27B, and idiopathic late-onset cerebellar ataxias

  • 期刊论文

  • 发表日期：

    2025年10月7日

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  • Leonardo E. Ariello,
  • Daniel R. Gold,
  • Jennifer L. Millar,
  • Michael C. Schubert,
  • Weiyi Mu,
  • Liana Rosenthal,
  • David P. W. Rastall

摘要

Background

RFC1-related CANVAS and FGF14-related SCA27B are recently recognized genetic causes of late-onset cerebellar ataxia (LOCA). Despite advances in genetic testing, most panels do not detect these intronic repeat expansions, often resulting in repeated testing, delayed diagnosis, and greater patient burden. Vestibular dysfunction is common in both disorders and may help differentiate them from idiopathic LOCA (ILOCA) subtypes, guiding targeted genetic testing.

Objectives

To evaluate whether vestibulo-ocular reflex (VOR) gain measured by video head impulse test (vHIT) can differentiate CANVAS and SCA27B from ILOCA.

Methods

We reviewed 290 records of individuals with suspected cerebellar ataxia at the Johns Hopkins Ataxia Center (2023–2025). VOR gains were assessed using vHIT and compared across groups. Diagnostic thresholds were determined using receiver operating characteristic curves, with significance set at p < 0.05.

Results

Fifth-nine participants were included: 10 CANVAS, 33 SCA27B, and 16 ILOCA, and matched with 31 controls. Bilateral vestibulopathy (VOR gain < 0.6) was present in 80% of CANVAS, 18% of SCA27B, and none of ILOCA (p = 0.024). Mean horizontal VOR gains were significantly lower in CANVAS (0.22) and SCA27B (0.85) than in ILOCA (1.11; p < 0.001). VOR gains < 0.70 differentiated CANVAS/SCA27B from ILOCA (100% specificity, 44% sensitivity), while a threshold of 0.50 distinguished CANVAS from SCA27B (91% specificity and 70% sensitivity).

Discussion

Reduced VOR gains were common in both CANVAS and SCA27B, and not observed in ILOCA. vHIT metrics may assist in distinguishing these genetic ataxias from ILOCA and each other, supporting potential utility as physiologic biomarkers and guiding targeted genetic testing.