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. 2025 Apr;15(2):e200427.
doi: 10.1212/CPJ.0000000000200427. Epub 2025 Jan 16.

Improving the Clinical Diagnostic Criteria for Genetically Confirmed Adult-Onset Huntington Disease: Considering Nonmotor Presentations

Ciaran M Considine  1 , Clare M Eddy  2   3 , Samuel A Frank  4 , Sandra K Kostyk  5 , Mayke Oosterloo  6 , Annie Killoran  7 , Erin Furr Stimming  8 , Matthias Dose  9 , Travis Cruickshank  10 , Thomas D Bird  11 , Louise Vetter  12 , Astri Arnesen  13 , James Valvano  14 , Herwig W Lange  15 , Daniel O Claassen  1
Affiliations

Improving the Clinical Diagnostic Criteria for Genetically Confirmed Adult-Onset Huntington Disease: Considering Nonmotor Presentations

Ciaran M Considine et al. Neurol Clin Pract. 2025 Apr.

Abstract

Background: Huntington disease (HD) is a genetic neurodegenerative disorder. Given the focus on motor manifestations, nonmotor symptoms are frequently underappreciated in clinical evaluations, despite frequently contributing to primary functional impairment.

Recent findings: A diagnosis of motor-onset as the definition of manifest symptoms misrepresents the complex nature of HD presentation. Despite recent attempt to integrate nonmotor diagnostic criteria, practical guidelines are necessary to inform clinical diagnosis. We propose an HD diagnostic framework and staging system that prioritizes genetic testing, integrates motor and nonmotor symptom considerations in the determination of clinical disease onset and severity, and acknowledges the secondary role of clinically indicated diagnostic assessments, incorporating the broad symptom profiles observed in clinical practice.

Implications for practice: The proposed diagnostic criteria more accurately reflect the presentation of HD and provide greater opportunities for health care professionals to provide appropriate clinical care guidelines for adults with gene-expanded HD.

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Conflict of interest statement

The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

Figures

Figure
Figure. Clinical Diagnosis of Genetically Confirmed Adult-Onset Huntington Disease
Proposed symptomatic categories for patients with abnormal CAG expansion and the absence of unequivocal motor signs of Huntington disease (HD).
See this image and copyright information in PMC

Comment in

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