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Features of Frontotemporal Dementia Linked to Chromosome 3

This study advances our understanding of the genetic basis and phenotypic variations of familial frontotemporal dementia.

Over a 17-year period, Gydesen and colleagues studied clinical and pathologic features in 22 individuals from a large kindred affected with autosomal-dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD-3). A neurologist and a psychiatrist evaluated the patients and performed the Mini-Mental State Exam and a small series of bedside cognitive tests. Seven CT scans, one MRI scan, 2 PET scans, and 2 autopsies were performed.

Age of onset varied between 46 and 65 years. The disease presented with a frontal lobe syndrome, but there was also evidence of dysfunction in the temporal and dominant parietal lobes. Prominent pyramidal and extrapyramidal disturbances were seen late in the illness. Structural and functional imaging revealed diffuse cortical atrophy and hypometabolism. Pathologic examination demonstrated cortical atrophy and gliosis without distinctive histopathology.

Comment: Autosomal-dominant FTD, like autosomal-dominant Alzheimer's disease (AD), has been associated with mutations on multiple chromosomes. The frontal lobe syndrome in these FTD-3 family members developed without the early, asymmetric frontal lobe degeneration, early parkinsonian features, and distinctive tau pathology seen in families with autosomal-dominant FTD with a locus on chromosome 17 (Am J Hum Genet 1994; 55:1159) and without the motor neuron disease seen in FTD linked to chromosome 9 (JAMA 2000; 284:4). The diffuse cortical involvement and generalized atrophy seen on CT scans in FTD-3 are hard to distinguish from AD, except that in FTD-3, the medial temporal lobe structures are relatively preserved on imaging and at autopsy. This report helps to clarify the relation between specific genetic mutations and phenotypic expressions in familial FTD. The ongoing study of this family would benefit from cognitive, behavioral, and neuroimaging evaluations that are standardized and serial.

— Stephen Salloway, MD, MS

Dr. Salloway is Chief of Neurology and the Memory Disorders Program, Butler Hospital, and Associate Professor, Department of Clinical Neurosciences, Brown Medical School, Providence, RI.

Published in Journal Watch Neurology January 10, 2003

Citation(s):

Gydesen S et al. Chromosome 3 linked frontotemporal dementia (FTD-3). Neurology 2002 Nov 26; 59:1585-94.

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