Natural history of Huntington disease

JAMA Neurol. 2013 Dec;70(12):1520-30. doi: 10.1001/jamaneurol.2013.4408.


Importance: Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials.

Objective: To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls.

Design, setting, and participants: Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n =4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease.

Main outcomes and measures: Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs.

Results: Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P < .001), and average pulse was higher (74.2 vs 69.6 beats/min; P < .001).

Conclusions and relevance: Over 3 years, the cardinal features of Huntington disease all declined in a monotonic manner. These data quantify the natural history of the disease and may inform the design of trials aimed at reducing its burden.

Trial registration: Identifier: NCT00313495.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Australia
  • Canada
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Disability Evaluation
  • Disease Progression*
  • Female
  • Humans
  • Huntingtin Protein
  • Huntington Disease / complications*
  • Male
  • Mental Disorders / etiology*
  • Middle Aged
  • Movement Disorders / etiology*
  • Nerve Tissue Proteins / genetics
  • Retrospective Studies
  • Severity of Illness Index
  • Trinucleotide Repeats / genetics
  • United States


  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins

Associated data