Clinical and Genetic Studies of Familial Presenile Dementia With Neuronal Inclusion Bodies

INCLUSION CRITERIA: Patients with a family history of early-onset progressive dementia or decline in cognition and neuronal inclusion bodies which are immunohistopathologically consistent with neuroserpin inclusion bodies. Children with progressive dementia and myoclonic epilepsy which is consistent with the reported clinical course in pediatric patients or children with the clinical phenotype who on autopsy demonstrate neuronal inclusion boidies which are immunohistopathologically consistent with neuroserpin inclusion bodies. Family members at risk, of at least 18 years of age, including first degree relatives of affected patients and the adult offspring of these first degree relatives. In rare instances probands and their at risk family members with known presenile dementia and a neurologic course typical of that seen in FENIB will be enrolled. We may also enroll offsite individuals who have any of the above findings, but are too medically fragile to travel to the Clinical Center and for whom a durable power of attorney (DPA) is available. The physical examination and laboratory research studies will be performed by the Investigator(s) and all clinical studies will be done in a local accredited hospital. Family members either not at risk and unaffected spouses may enroll primarily for genetic linkage information. These individuals will contribute a blood sample for molecular analysis only. Those unwilling to travel may also provide a blood sample only. No clinical studies will be performed on individuals from this category. EXCLUSION CRITERIA: Another diagnosis of presenile demential is made by a physician including but not limited to: 1) Huntington Disease, 2) Parkinson Disease/Diffuse Lewy Body Disease, 3) Familial Alzheimer Disease with known mutations in presenilin 1, presenilin 2 or beta-amyloid precursor protein, 4) Lafora Body Disease, 5) Pick's Disease, and 6) fronto-temporal dementia. A Durable Power of Attorney is not available in a human subject that is not medically competent to give consent.