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Cerebral Amyloid Angiopathy

OMIM ID:

autosomal dominant

Cerebral Amyloid Angiopathy

Alternate Names

familial Danish dementia
FDD

Defective Genes

ITM2B

Clinical Characteristics

Ocular Features

Posterior polar cataracts appear during the third decade of life.

Systemic Features

Progressive hearing loss has its onset in the third decade and becomes severe in the 5th decade.  Progressive dementia, often in the form of paranoid psychosis, begins about age 50.  Cerebellar ataxia and intention tremor have their onset in midlife.  There is a diffuse atrophy throughout the brain and cranial nerves are demyelinated.  Blood vessels throughout the CNS, spinal cord and retina show an amyloid angiopathy.  Intracranial hemorrhage is a significant risk and, when lobar in location, carries a significant risk of mortality within months.  Death generally occurs in the 5th and 6th decades of life.

Genetics

Inheritance

Pedigree patterns in the few reported families are consistent with autosomal dominant inheritance.  A mutation has been found in the ITM2B gene located at 13q14.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

No treatment is available.

Selected Resources

Publications

Displaying 1 - 5 of 5

A decamer duplication in the 3′ region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred

PubMedID: 10781099

CATARACT, DEAFNESS, CEREBELLAR ATAXIA, PSYCHOSIS AND DEMENTIA-A NEW SYNDROME

PubMedID: 5457846

Dementia is strongly associated with 90-day mortality in lobar cerebral amyloid angiopathy related intra-cerebral haemorrhage

PubMedID: 22883482

Heredopathia ophthalmo-oto-encephalica

PubMedID:

The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy

PubMedID: 22565298