Phenotype/Genotype Correlations in Movement Disorders
Phenotype/Genotype Correlations in Movement Disorders
The goal of this protocol is to identify families with inherited movement disorders and
 evaluate disease manifestations to establish an accurate clinical diagnosis by using newest
 technological advances and investigate the underlying molecular mechanisms. Studies of
 inherited movement disorders in large families with good genealogical records are especially
 valuable. 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 responsible for a specific disorder.
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