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.
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.
- 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
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.
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
A Durable Power of Attorney is not available in a human subject that is not medically
competent to give consent.