Clinical trial NCT00018889: Phenotype/Genotype Correlations in Movement Disorders
Official title: Phenotype/Genotype Correlations in Movement Disorders
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Movement Disorder
Keywords: Clinical Evaluation
Genetic Study
Essential Tremor
Familial Myoclonus
Hereditary Ataxia
Natural History
Movement Disorder
Inherited Movement Disorder
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2001-07-09
Enrollment: 2500
Sex: ALL
Minimum age (years): 2
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

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.

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
* 000865: Natural history of movement disorders
* 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.

Eligibility criteria: * INCLUSION CRITERIA:
* Individuals with suspected movement disorders
* Family members of movement disorders patients
* Ability to give informed consent or have a legally authorized representative able to give consent (for adults without consent capacity) or parent/guardian able to provide informed consent (for a child)
* If unable to give informed consent, ability to give assent (for children or adults without consent capacity)
* NIH Employees can participate in this study if they meet eligibility.

EXCLUSION CRITERIA:

* Pregnant women
* Children less than 2 years of age
* Employees of the Parkinson's Disease Clinic, NINDS

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 or 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
* Under 12 years of age

There is no general exclusion for NIH employees.

Primary outcomes:
measure: The primary outcome measure is the phenotypic and genotypic characterizations of patients and family members with movement disorders.
timeFrame: 10 Years
Secondary outcomes:
measure: Identification of disease-specific biomarkers in stem cells derived from patient peripheral blood mononuclear cells or fibroblast lines
timeFrame: Study end
measure: Identification of new genes and/or peripheral blood biomarkers associated with movement disorders
timeFrame: Study end
measure: Identification of new genes and/or peripheral blood biomarkers associated with movement disorders.
timeFrame: Study end
measure: Establishment of a clinical diagnosis (when possible)
timeFrame: Study end
measure: Referral of patients and/or family members for participation in other NIH studies
timeFrame: Study end
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
name: Debra J Ehrlich, M.D.
role: PRINCIPAL_INVESTIGATOR
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