Phenotype/Genotype Correlations in Movement Disorders

Study Overview
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Brief Summary
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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
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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 93-N-0202 Diagnosis and natural history protocol for patients with different neurological conditions 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) 18-N-0140: Clinical Laboratory Evaluation of Chronic Autonomic Failure 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.

Official Title
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Phenotype/Genotype Correlations in Movement Disorders

Conditions
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Movement Disorder

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Individuals with 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 will be excluded from MRI or X-ray studies Children less than 2 years of age Employees of the Parkinsons 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 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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Patients age 2 years and older with a clinical or suspected diagnosis of movement disorder | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure is the phenotypic and genotypic characterizations of patients and family members with movement disorders. | Characterizations to determine their eligibility for inclusion in other NIH protocols. | 10 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Study end | 
| Identification of peripheral alpha-synuclein via histology of skin biopsies |  | Study end | 
| 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. |  | Study end | 
| Identification of new genes and/or peripheral blood biomarkers associated with movement disorders. |  | Study end | 
| Identification of disease-specific biomarkers in stem cells derived from patient peripheral blood mononuclear cells or fibroblast lines. |  | Study end | 
| Identification clinical correlations between phenotype and genotype |  | Study end | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Evaluation, Genetic Study, Essential Tremor, Familial Myoclonus, Hereditary Ataxia, Natural History, Movement Disorder, Inherited Movement Disorder