Enroll -HD: A Prospective Registry Study in a Global Huntington's Disease Cohort

The primary objective of Enroll-HD is to develop a comprehensive repository of prospective
and systematically collected clinical research data (demography, clinical features, family
history, genetic characteristics) and biological specimens (blood) from individuals with
manifest HD, unaffected individuals known to carry the HD mutation or at risk of carrying the
HD mutation, and control research participants (e.g., spouses, siblings or offspring of HD
mutation carriers known not to carry the HD mutation). Enroll-HD is conceived as a
broad-based and long-term project to maximize the efficiencies of non-clinical research and
participation in clinical research. With over 200 sites in roughly 30 countries, Enroll HD
will be the largest database available for HD researchers.

Inclusion Criteria:

- Carriers: This group comprises the primary study population and consists of
individuals who carry the HD gene expansion mutation.

- Controls: This group comprises the comparator study population and consists of
individuals who do not carry the HD expansion mutation.

These two major categories can be further subdivided into six different subgroups of
eligible individuals:

- Manifest/Motor-manifest HD: Carriers with clinical features that are regarded in the
opinion of the investigator as diagnostic of HD.

- Pre-Manifest/-Motor-manifest HD: Carriers without clinical features regarded as
diagnostic of HD.

- Genotype Unknown: This group includes a first or second degree relative, i.e., related
by blood to a carrier, who has not undergone predictive testing for HD and therefore
has an undetermined carrier status.

- Genotype Negative: This group includes a first or second degree relative, i.e.,
related by blood to a carrier, who has undergone predictive testing for HD and is
known not to carry the HD expansion mutation.

- Family Control: Family members or individuals not related by blood to carriers (e.g.,
spouses, partners, caregivers).

- Community Controls: Individuals unrelated to HD carriers who did not grow up in a
family affected by HD. Data collected from community controls will be used for
generation of normative data for sub-studies.

Participant status will be captured in the study database using 2 variables: 1)
Investigator Determined Status: this will be based on clinical signs and symptoms and
genotyping performed as part of medical care, and will be updated at every visit and 2)
Research Genotyping Status: this will be based on genotyping conducted as part of Enroll-HD
study procedures. Based on research genotyping, participants will be reclassified under
this variable from Genotype Unknown to 'Carriers' or 'Controls'. Investigators and
participants will be blinded to this reclassification.

Exclusion Criteria:

- Individuals who do not meet inclusion criteria,

- Individuals with choreic movement disorders in the context of a negative test for the
HD gene mutation.

- For Community Controls: those individuals with a major central nervous system disorder
will be excluded (e.g. stroke, Parkinson disease, Multiple Sclerosis, etc.).

Participants under 18 may be eligible to participate (if they have juvenile-onset HD).