Phenotype/Genotype Correlations in Movement Disorders

Objective:

The goal of this protocol is to identify families with inherited movement disorders and
evaluate disease manifestations to establish an accurate clinical diagnosis, and to
investigate the underlying molecular mechanisms. Studies of inherited movement disorders in
large families with good genealogical records are especially valuable.

Additionally, the plan is to screen subjects with and without Parkinson's disease for the
presence of revelant antibodies, such as antibodies targeting tobacco mosaic virus antigens
which may have a protective role against the development of the disease or may be related to
other pathophysiologic mechanisms.

The study will also assess a series of exploratory peripheral blood biomarkers, including,
but not limited to, those delineated by DNA, RNA, protein, and/or metabolite alterations in
an effort to more accurately predict those with, or at risk of having, the specific
neurological disease. Finally, validation of the NIH Toolbox Odor Identification Test
(NIHOIT) against the standard University of Pennsylvania Smell Identification Test (UPSIT) in
patients with Parkinson's Disease will be analyzed.

Study population:

Subjects older than 2 years old with movement disorders and their family members will be
enrolled. Patients with diseases of known molecular basis will be genotyped in order to
investigate phenotype/genotype correlation. Patients with disease of unknown or incomplete
genetic characterization will be studied with a hope of contributing to the identification of
specific disease causing genes and genetic mechanisms and/or peripheral biosignatures
involved in a particular disorder.

Design:

Eligible participants will have an initial medical and/or neurological evaluation at the
Clinical Center or in the field, including blood draw for genetic and other biomarker
testing.

Outcome measures:

Determination of phenotype/genotype correlations in specific movement disorders, gene
identification if not known, gene expression and protein and metabolite levels, and presence
of antibodies in Parkinson's disease and establishment of a clinical diagnosis when possible.

- INCLUSION CRITERIA:

Individuals with known or suspected inherited movement disorders.

Family members of movement disorders patients

EXCLUSION CRITERIA:

Pregnant women will be excluded from MRI or X-ray studies

Children less than 2 years of age

Those who cannot provide their own consent or appoint a Durable Power of Attorney (DPA).

Exclusion criteria for MRI

- Presence of metal in subject's body which would make having an MRI scan unsafe, such
as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial
heart valves, cochlear implants, shrapnel fragments, or if subject was a welder or
metal worker (since small metal fragments in the eye may be present).

- Subject is uncomfortable in small closed spaces (have claustrophobia) so that they
would feel uncomfortable in the MRI machine.

- Unable to lie comfortably on back for up to 1 hour.

- Are pregnant

- Under 12 years of age