genetic characterization of movement disorders and dementias

Conditions: Dementia; Movement Disorder

Summary: background: there are two basic types of movement disorders. some cause excessive movement, some cause slowness or lack of movement. some of these are caused by mutations in genes. on the other hand, dementia is a condition of declining mental abilities, especially memory. dementia can occur at any age but becomes more frequent with age. researchers want to study the genes of families with a history of movement disorders or dementia. they hope to find a genetic cause of these disorders. this can help them better understand and treat the diseases. this study will not be limited to a particular disorder, but will study all movement disorders or dementias in general. this study will perform genetic testing to identify the genetic causes of movement disorders and dementia. today, genetic testing can be done to analyze multiple genes at the same time. this increases the chances of finding the genetic cause of movement disorders and dementias. objectives: to learn more about movement disorders and dementia, their causes, and treatments. eligibility: adults and children with a movement disorder or dementia, and their family members. healthy volunteers. design: participants will be screened with medical history and blood tests. some will have physical exam. participants will give a blood sample by a needle in the arm. this can be done at the clinic, by their own doctor, or at home. alternatively, a saliva sample may be provided if a blood sample cannot be obtained. participants can opt to send an extra blood sample to a repository for future study. genetic test will be done on these samples. the samples will be coded. the key to the code will remain at nia. only nia investigators will have access to the code key. participants can request to receive results of the tests. participation is generally a single visit. participants may be called back for extra

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.

Eligibility criteria:
* 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.

Keywords: movement disorders polymorphisms dna lymphoblastoid cell lines natural history