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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    ABSTRACT: There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the initial presenting symptoms across dementia subtypes. For this reason, reliable markers are of considerable diagnostic value. Communication disorders have proven to be among the strongest predictors for discriminating among dementia subtypes. As such, speech-language pathologists may be poised to make an increasingly visible contribution to dementia diagnosis and its ongoing management. The value and durability of this potential contribution, however, demands an improved discipline-wide knowledge base about the unique features associated with different dementia variants. To this end we provide an overview of cognition, language, and clinical pathological features of four of the most common non-Alzheimer's dementias: frontotemporal dementia, vascular dementia, Lewy body disease dementia, and Parkinson's disease dementia. Learning outcomes: Readers will learn characteristics and distinguishing features of several non-Alzheimer's dementias, including Parkinson's disease dementia, frontotemporal dementia, vascular dementia, and Lewy body dementia. Readers will also learn to distinguish between several variants of frontotemporal dementia. Finally, readers will gain knowledge of the term primary progressive aphasia as it relates to the aforementioned dementia etiologies.
    Journal of Communication Disorders 09/2010; 43(5):438-52. DOI:10.1016/j.jcomdis.2010.04.011 · 1.45 Impact Factor
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    • "Second, Goldman and colleagues (2004) noted that families affected by FTD seem to be psychologically damaged. Psychological damage may occur as a consequence of having an FTD- affected parent; FTD patients have inhibition problems. "
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    ABSTRACT: A decade of genetic counseling of frontotemporal dementia (FTD) affected families has generated two important observations. First, the uptake rate for presymptomatic testing for FTD is low in our department of Clinical Genetics at the Erasmus Medical Center in the Netherlands. Second, FTD at-risk counselees reported substantial familial opposition to genetic testing, which is distinct from the attitude in Huntington Disease affected families. We hypothesize that the low acceptance for FTD genetic counseling is consequential to the familial opposition and explain this within the theoretical framework of separation-individuation. Furthermore, we hypothesize that separation-individuation problems do not similarly influence the acceptance of HD genetic counseling, due to the educative role of the well-organised patient organization for HD in the Netherlands. We offer counseling recommendations that serve to facilitate the individuation of the counselee with respect to the FTD genetic test.
    Journal of Genetic Counseling 05/2009; 18(4):350-6. DOI:10.1007/s10897-009-9222-3 · 2.24 Impact Factor
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    ABSTRACT: Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that affects frontal and temporal regions of the brain. Two proteins indicated in the pathology are tau and the recently discovered TDP-43. Major manifestations include progressive aphasia and a disorder of social comportment. The diagnosis of a patient includes a detailed cognitive exam, clinical testing, and neuroimaging techniques. The current goal of therapy for FTLD is symptomatic management with medications borrowed from other conditions. Nonpharmacologic management such as behavioral interventions and environmental engineering are also efficacious in optimizing quality of life.
    American Journal of Alzheimer s Disease and Other Dementias 05/2008; 23(2):125-31. DOI:10.1177/1533317507307961 · 1.63 Impact Factor
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