Frontotemporal dementia: genetics and genetic counseling dilemmas.

Memory and Aging Center, University of California, San Francisco, Department of Neurology, San Francisco, California 94143-1207, USA.
The Neurologist (Impact Factor: 1.16). 10/2004; 10(5):227-34.
Source: PubMed


Frontotemporal dementia (FTD) is a neurodegenerative disease with early symptoms of personality change and/or language disorder. Approximately 40% of individuals with FTD have a family history of dementia; however, in our experience, less than 10% have clear autosomal dominant inheritance. Mutations in the microtubule-associated protein tau (MAPT) gene have been reported in up to 50% of hereditary cases, but are unusual except in families with more than 3 individuals with FTD. The genetics of FTD is complicated by clinical heterogeneity, variable expression, phenocopies, misdiagnoses, and lost family histories. The objective of this paper is to enable physicians to recognize hereditary patterns and genetic concerns of FTD families and to understand genetic counseling strategies.
The complexity of FTD genetics and genetic counseling are illustrated using 4 case histories. Case 1 demonstrates the difficulty obtaining a reliable FTD family history. Case 2 illustrates how psychiatric phenocopies can make family linkage studies difficult. The lack of genotype and phenotype correlation and issues of predictive genetic testing within FTD families are the subject of case 3, and case 4 shows how normal aging language difficulties and cognitive changes can be misinterpreted when a family history of dementia is present.
Physicians seeing patients with possible FTD should be aware of the risk of a genetic etiology. A 3-generation family history should be obtained with attention to neurologic, psychiatric, and behavioral symptoms. Variable expression and phenocopies are confounding factors when assessing a possible genetic etiology. Referral of the patient and family for genetic counseling is recommended.

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Available from: Jill Goldman, Apr 15, 2014
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    • "However, abnormal aggregations of these proteins destroy neurons. Recent Author's personal copy histopathlogical confirmation studies suggest that other neurodegenerative diseases such as corticobasal degeneration (CBD), Parkinsonism, progressive supranuclear palsy (PSP), motor neuron disease (MND) and amyotrophic lateral sclerosis (ALS) may all share a common protein pathology (i.e., TDP-43) (Bian & Grossman, 2007; Goldman et al., 2004; Miller, 2007). There are at least three distinct FTD phenotypes, each having a particular distribution of cortical damage. "
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