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

Last updated: June 30, 2017
Sponsor: National Human Genome Research Institute (NHGRI)
Overall Status: Completed

Phase

N/A

Condition

Dementia

Unverricht-lundborg Syndrome

Treatment

N/A

Clinical Study ID

NCT00006176
000191
00-HG-0191
  • Ages > 10
  • All Genders

Study Summary

The purpose of this study is to learn more about the medical problems and the genetic factors involved in a recently defined form of inherited dementia called "familial dementia with neuroserpin inclusion bodies (FDNIB)." Abnormal substances in nerve cells of patients with this disease affect brain and nervous system function, causing confusion, memory decline and impaired cognition (thinking ability). Patients also develop movement disorders and, possibly, seizures. Symptoms begin in midlife, between 45 and 55 years of age.

Patients with FDNIB and family members 18 years of age or older at risk for the disease may be eligible for this 3-year study.

Participants will have a medical and family history and review of medical records; interview with a medical geneticist (specialist in genetics); physical, neurological and psychiatric examinations; and the following tests and procedures:

  1. Blood tests to assess general health

  2. Chest and skull X-rays

  3. Electrocardiogram (EKG)-record of the electrical activity of the heart using electrodes placed on the chest

  4. Electroencephalogram (EEG)-record of the electrical activity of the brain using electrodes placed on the head

  5. Ultrasound of the abdomen-imaging of abdominal organs using sound waves

  6. Brain magnetic resonance imaging (MRI)-imaging of the brain using a strong magnetic field and radio waves

  7. Hearing evaluation

  8. Assessment of performance of daily living activities

  9. Single photon emission computed tomography (SPECT)-imaging of brain metabolism and blood flow using a radioactive substance injected into a vein

The evaluation will be done over a 3- to 4-day period. At their completion, participants will meet with a physician and a genetics counselor to discuss the clinically significant findings. Participants may be asked to return for follow-up evaluations every 6 months to a year (depending on the individual's condition) for 3 years.

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA: Patients with a family history of early-onset progressive dementia or decline in cognitionand neuronal inclusion bodies which are immunohistopathologically consistent withneuroserpin inclusion bodies. Children with progressive dementia and myoclonic epilepsy which is consistent with thereported clinical course in pediatric patients or children with the clinical phenotype whoon autopsy demonstrate neuronal inclusion boidies which are immunohistopathologicallyconsistent with neuroserpin inclusion bodies. Family members at risk, of at least 18 years of age, including first degree relatives ofaffected patients and the adult offspring of these first degree relatives. In rare instances probands and their at risk family members with known presenile dementiaand 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 toomedically 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 beperformed by the Investigator(s) and all clinical studies will be done in a localaccredited hospital. Family members either not at risk and unaffected spouses may enroll primarily for geneticlinkage information. These individuals will contribute a blood sample for molecularanalysis only. Those unwilling to travel may also provide a blood sample only. No clinicalstudies will be performed on individuals from this category.

Exclusion

EXCLUSION CRITERIA: Another diagnosis of presenile demential is made by a physician including but not limitedto: 1) Huntington Disease, 2) Parkinson Disease/Diffuse Lewy Body Disease, 3) FamilialAlzheimer Disease with known mutations in presenilin 1, presenilin 2 or beta-amyloidprecursor protein, 4) Lafora Body Disease, 5) Pick's Disease, and 6) fronto-temporaldementia. A Durable Power of Attorney is not available in a human subject that is not medicallycompetent to give consent.

Study Design

Total Participants: 100
Study Start date:
August 10, 2000
Estimated Completion Date:
August 04, 2009

Study Description

This project involves the study of a novel familial neurodegenerative disorder, familial encephalopathy with neuroserpin inclusion bodies (FENIB). This disorder, which has a characteristic clinical course of progressive dementia and neurologic involvement, was initially defined in one extended family. Neuroserpin is the gene for this disorder and a mutation is present in this large kindred and four additional families/cases. This protocol will characterize the clinical phenotype, delineate the natural history of the disorder and explore genotype/phenotype correlations in the index family and possibly in other reported cases. Families with immunohistopathologically-neuroserpin positive neuronal inclusions on autopsy/biopsy in an affected member(s), neuroserpin mutation-positive proband, or with familial presenile dementia with neurologic features consistent with the original FENIB family will be enrolled.

Connect with a study center

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland 20892
    United States

    Site Not Available

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