Genetic Characterization of Movement Disorders and Dementias

Objective

The objective of this study is to ascertain individuals with a clinical diagnosis of a movement disorder or dementia, their affected and unaffected family members, and unrelated, healthy individuals (to provide control samples); to characterize their phenotypes; and to identify and further characterize genetic contributions to etiology by collecting blood samples, and/or saliva samples on these individuals for DNA and induced Pluripotent stem (iPs) cell line preparation.

Study population

Up to 10,000 persons with a diagnosis of a movement disorder or dementia, 1,000 asymptomatic persons who are family members/related to individuals with a diagnosis of movement disorder or dementia, and 1,000 unrelated, healthy control individuals.

Design

This study usually requires one outpatient visit to the NIH Clinical Center. Participant visits may also take place when they are an inpatient at the NIH Clinical Center. Those who are unable to travel to NIH may have study procedures performed at a site near their

home, such as hospital facilities, private physician offices, nursing homes, assisted living facilities, local community centers, or participant homes. Participants will undergo medical record review, a physical examination and biospecimen collection including

blood draw and/or saliva collection at the enrollment visit.

Additional visits may be scheduled to collect additional phenotype information or to collect additional biospecimens.

Outcome measures

The primary outcome measure of this study is the identification of pathogenic genetic variants that are causative for the movement disorder or dementia that the patient has been diagnosed with. These disease-causing variants are often inherited.

The secondary outcome measure of this study is the identification of genetic variants that alter susceptibility/risk for the movement disorder or dementia that the patient has been diagnosed with. These genetic risk factors are associated with disease that can be apparently sporadic in nature.

• INCLUSION CRITERIA

For Patients:

• Diagnosis of a movement disorder or dementia by a neurologist or other qualified professional and accompanied by sufficient clinical and/or laboratory evidence to support the diagnosis
• Confirmation of a movement disorder or dementia by study investigators or a qualified clinician by physical examination and/or review of medical records
• Ages 18 and above
• Able to provide consent or, in the case of minors, or cognitive impairment, have a legally-authorized representative to provide consent
• Able to understand and participate in study procedures or for those without consent capacity, able to participate in study procedures AND has a legally authorized representative that understands the study procedures and can consent on their behalf.

For unaffected family members of patients:

• Unaffected relative of a patient diagnosed with a movement disorder or dementia enrolled in this protocol. For these purposes, we define a family member as an individual for which there is a demonstrable relationship with the proband in the pedigree. This is a standard approach used in family-based studies. Furthermore, the related patient (defined as a family member diagnosed with the disease of interest) must be enrolled in the study.
• Ages 18 and above
• Able to provide consent
• Able to understand and participate in study procedures

For unrelated healthy control individuals:

• Be in good general health
• Have no known movement disorder or dementia, or family member with a movement disorder or dementia
• Age 18 and above
• Able to provide consent
• Able to understand and participate in study procedures

Exclusion criteria

For patients:

-An identifiable, non-genetic etiology for the movement disorder or dementia, such as a specific environmental exposure, birth injury, metabolic disorder, or brain infection such as encephalitis

For all participants:

• Clinically significant anemia that would make phlebotomy unsafe, and participant unwilling to provide saliva sample.
• Clinically significant bleeding that would make phlebotomy unsafe, and participant unwilling to provide saliva sample.
• Any medical condition that would make phlebotomy unsafe or undesirable, such as a serious medical illness like unstable heart disease, or unstable chronic obstructive pulmonary disease, and participant unwilling to provide saliva sample.