Age of onset and behavioral manifestations in Huntington's disease: An Enroll-HD cohort analysis

Clin Genet. 2021 Jan;99(1):133-142. doi: 10.1111/cge.13857. Epub 2020 Oct 16.


Huntington's disease is associated with motor, cognitive and behavioral dysfunction. Behavioral symptoms may present before, after, or simultaneously with clinical disease manifestation. The relationship between age of onset and behavioral symptom presentation and severity was explored using the Enroll-HD database. Manifest individuals (n = 4469) were initially divided into three groups for preliminary analysis: early onset (<30 years; n = 479); mid-adult onset (30-59 years; n = 3478); and late onset (>59 years; n = 512). Incidence of behavioral symptoms reported at onset was highest in those with early onset symptoms at 26% (n = 126), compared with 19% (n = 678) for mid-adult onset and 11% (n = 56) for late onset (P < 0.0001). Refined analysis, looking across the continuum of ages rather than between categorical subgroups found that a one-year increase in age of onset was associated with a 5.6% decrease in the odds of behavioral symptoms being retrospectively reported as the presenting symptom (P < 0.0001). By the time of study enrollment, the odds of reporting severe behavioral symptoms decreased by 5.5% for each one-year increase in reported age of onset. Exploring environmental, genetic and epigenetic factors that affect age of onset and further characterizing types and severity of behavioral symptoms may improve treatment and understanding of Huntington's disease's impact on affected individuals.

Keywords: Huntington's disease; age of onset; behavior; phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Behavioral Symptoms / epidemiology
  • Behavioral Symptoms / genetics*
  • Behavioral Symptoms / physiopathology
  • Cognitive Dysfunction / epidemiology
  • Cognitive Dysfunction / genetics*
  • Cognitive Dysfunction / physiopathology
  • Cohort Studies
  • Disease Progression
  • Epigenomics
  • Female
  • Humans
  • Huntington Disease / epidemiology
  • Huntington Disease / genetics*
  • Huntington Disease / physiopathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index