Phenotype/Genotype Correlations in Movement Disorders

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT00018889

Collaborator

(none)

2,500

Enrollment

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Movement Disorder

Detailed Description

Objective: The primary objective of this study is to perform phenotypic and genotypic characterizations of patients and family members with a known or suspected diagnosis of a movement disorder and screen for eligibility to participate in other movement disorder related protocols:

14-N-0086 Deep brain stimulation therapy in movement disorders
11-N-0211 Deep brain stimulation surgery for movement disorders
12-N-0031 Imaging biomarkers in Parkinson s Disease
93-N-0202 Diagnosis and natural history protocol for patients with different neurological conditions
17-N-0076: Does N-Acetylcysteine decrease spontaneous oxidation of central neural dopamine in Parkinson s Disease?
17-N-0035: Clinical and physiological studies of tremor syndromes
00-N-0043: Clinical and molecular manifestations of inherited neurologic disorders
03-AG-N-329 (NIA): The genetic characterization of movement disorders and dementias
20M0082 Phase 1 Study: PET Imaging of Cyclooxygenases in Neurodegenerative Brain Disease; Institute (NIMH)

The secondary goals of this protocol are to learn more about genetic causes of movement disorders and their phenotypic associations; identify patients and families with inherited movement disorders; 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 well-documented genealogical records are especially valuable. The study will also assess a series of exploratory peripheral 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.

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 correlations. 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 bio-signatures involved in a particular disorder.

Design:

This is an observational diagnostic study of movement disorders and their progression and pathophysiology.

Outcome measures: Determination of phenotype/genotype correlations in specific movement disorders, referral of patients and/or family members for participation in other NIH studies, gene identification if not known, gene expression and protein, metabolite and nucleic acid levels, collection of blood cells and generation of induced pluripotent stem cell lines, and establishment of a clinical diagnosis when possible.

Study Design

Study Type:

Observational

Anticipated Enrollment :

2500 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

Phenotype/Genotype Correlations in Movement Disorders

Actual Study Start Date :

Oct 22, 2001

Arms and Interventions

Arm	Intervention/Treatment
1 Patients age 2 years and older with a clinical or suspected diagnosis of movement disorder

Outcome Measures

Primary Outcome Measures

The primary outcome measure is the phenotypic and genotypic characterizations of patients and family members with movement disorders. [10 Years]
Characterizations to determine their eligibility for inclusion in other NIH protocols.

Secondary Outcome Measures

Identification of specific peripheral blood biomarkers in plasma of patients with or without PD that would improve the diagnostic accuracy, especially in subjects at risk of developing the disorder in the future []
Identification of peripheral alpha-synuclein via histology of skin biopsies []
Identification of new genes through newer techniques such as whole exome and whole genome to identify the genetic cause of a neurologic condition in an individual or family. []
Identification of new genes and/or peripheral blood biomarkers associated with movement disorders. []
Identification of disease-specific biomarkers in stem cells derived from patient peripheral blood mononuclear cells or fibroblast lines. []
Identification clinical correlations between phenotype and genotype []

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

There is no general exclusion for NIH employees. Inclusion/exclusion criteria will be checked before enrollment in each sub-study to ensure that participants remain eligible.