A Phenotypic Atlas for Huntington Disease Based on Data From the Enroll-HD Cohort Study

Area of Science:

• Genetics
• Neurology
• Clinical Research

Background:

• Huntington disease (HD) is characterized by CAG repeat expansion in the huntingtin gene, influencing motor dysfunction onset.
• The broader phenotype of HD, including non-motor features, across varying CAG lengths, ages, and functional statuses, requires further characterization.

Purpose of the Study:

• To develop a comprehensive phenotype atlas for Huntington disease using data from the Enroll-HD observational study.
• To summarize the range, distribution, outliers, and clusters of HD phenotypes across different CAG repeat lengths, age groups, and functional levels.

Main Methods:

• Utilized data from the Enroll-HD prospective longitudinal observational study, including 42,840 visits from 15,982 individuals with HD.
• Analyzed routine motor, cognitive, psychiatric, and functional measures, creating 223 age-by-CAG subsets for CAG repeat lengths 36-69 and 5-year age brackets.
• Developed the Enroll-HD Phenotype Atlas (EHDPA) based on data collected through October 31, 2020.

Main Results:

• The EHDPA provides a detailed summary of HD phenotypes across all disease domains.
• It includes data for CAG repeat lengths from 36 to 69 and age brackets from 20-24 to 85-89 years.
• The atlas is accessible online for researchers and clinicians.

Conclusions:

• The EHDPA offers a valuable tool for tracking HD progression and understanding phenotypic features associated with functional decline.
• It facilitates discussions on prognosis and may stimulate further research into multidomain characterization of HD progression and disease modifiers.