Inheritance of Frontotemporal Dementia

Chow, Tiffany W.; Miller, Bruce L.; Hayashi, Vivian N.; Geschwind, Daniel H.

doi:10.1001/archneur.56.7.817

Cited by 204 publications

(130 citation statements)

References 36 publications

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“…Chow et al (Chow, Miller, Hayashi, & Geschwind, 1999) investigated the frequency of familial FTD by looking for FTLD-related symptoms in the families of 42 index cases of FTD. After excluding family members with depression, they found familial cases in 40%, of whom the majority showed a dominant transmission pattern.…”

Section: Etiology Of Ftldmentioning

confidence: 99%

The Early Neuropsychological and Behavioral Characteristics of Frontotemporal Dementia

et al. 2008

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Frontotemporal lobe dementias (FTLD) represent a constellation of disorders that may be overlooked or misdiagnosed, despite being a fairly common presenile neurodegenerative diseases. Although the cognitive disorder can be difficult to document, particularly early in the dementia course, neuropsychological evaluation can assist in the diagnosis. Neuropsychologists are in an excellent position to draw from related disciplines like personality theory and social psychology to better assess the types of changes that characterize the prodromal and early phases of the disease. This review summarizes the current state of the field in the diagnosis of FTLD and discusses the emerging role of neuropsychology in elucidating the brain organization of complex processes including empathy, behavioral control and inhibition, reward systems, appetitive behaviors, emotional regulation, and goal-orientation. As this review underscores, FTD remains a powerful model for studying brain-behavior relationships.Frontotemporal lobar degeneration (FTLD) refers to a set of neurodegenerative disorders arising from relatively circumscribed frontal and temporal lobar atrophy. Characterized by troubling and progressive changes in behavior, personality, judgment, language, and cognition, the disorder compromises individuals while still in their productive years and may initially be mistaken as a psychiatric disorder. As with other degenerative dementias, a goal is to identify these disorders early with the intent of intervening before the disease has fully expressed in brain. Although no pharmacological treatments are yet available to prevent the disease progression, there are treatments that help alleviate symptoms and nonpharmacological interventions to deal with problem behaviors, coping, and adjustment. From a cognitive neuroscience perspective, the FTLD dementias with their effects on some of the core features of human personality and cognition offer an opportunity to better understand how these fundamental processes of human existence are functionally organized, both the processes involved as well as the brain systems that mediate them. This review article discusses the clinical presentation of the FTLD dementias with an emphasis on its early expression. We propose that by applying a theoretical framework of human behavior from social psychology and constructs from personality theory to the study of FTLD, neuropsychology is ideally positioned to elucidate some of the brain mechanisms underlying a range of complex human behaviors, emotions, and social cognition. Clinical and Neuropathological Expression of FTLDThe first mention of FTLD as a syndrome was in 1892 when Arnold Pick, a neurologist at the University of Prague, described the clinical and pathological features of one of his patients. He reported an aphasic presentation that progressed over three years in a 71-yearold individual. Upon autopsy, there was found to be significant frontal and temporal lobe atrophy in the diseased brain. Pick's clinical description of his patien...

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Section: Etiology Of Ftldmentioning

confidence: 99%

The Early Neuropsychological and Behavioral Characteristics of Frontotemporal Dementia

et al. 2008

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“…Up to 50% of FTD patients have a positive family history of dementia, mainly with autosomal dominant inheritance [Chow et al, 1999;Poorkaj et al, 2001;Rosso et al, 2003]. The majority of FTD families have been linked to chromosome 17q21.…”

Section: Introductionmentioning

confidence: 99%

Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia

et al. 2007

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Null mutations in the progranulin gene (GRN, PGRN) were recently identified as the causal mechanism underlying frontotemporal dementia (FTD) with ubiquitin-positive brain pathology linked to chromosome 17 (FTDU-17). In a Belgian and French FTD series comprising 332 patients, we reported 13 PGRN null mutations which were mainly nonsense and frameshift mutations resulting in premature stop codons. Here we report in the same patient series three missense mutations of which two (c.743C>T, p.Pro248Leu and c.1294C>T, p.Arg432Cys) were predicted in silico to severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency. In addition, we observed three sequence variations in the 5' regulatory region that might potentially affect PGRN transcription activity. Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD.

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“…In ϳ30 -50% of individuals, a family history of loosely defined dementia is present, some of these displaying an autosomal dominant pattern of inheritance (7,16,22,(25)(26)(27). In 1994, linkage to chromosome 17 was first established in a pedigree with a form of FTD designated disinhibitiondementia-parkinsonism-amyotrophy complex (28 ).…”

Section: Genetics Of Frontotemporal Dementiamentioning

confidence: 99%

“…This is especially important if an assay is being used for predictive testing. In the case of FTDP-17 mutations, the penetrance is reported to be very high by the sixth decade of life (7 ). Each laboratory is currently not required under CLIA to individually establish clinical validity for a genetic test; it is considered acceptable to rely on external validation reported in peer-reviewed literature (67 ).…”

Section: From Research To Clinical Testingmentioning

confidence: 99%

Familial Frontotemporal Dementia: From Gene Discovery to Clinical Molecular Diagnostics

et al. 2003

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Genetic testing is important for diagnosis and prediction of many diseases. The development of a clinical genetic test can be rapid for common disorders, but for rare genetic disorders this process can take years, if it occurs at all. We review the path from gene discovery to development of a clinical genetic test, using frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) as an example of a complex, rare genetic condition. An Institutional Review Boardapproved multidisciplinary research program was developed to identify patients with familial frontotemporal dementia. Genetic counseling is provided and DNA obtained to identify mutations associated with FTDP-17. In some cases it may be appropriate for individuals to be given the opportunity to learn information from the research study to prevent unnecessary diagnostic studies or the utilization of inappropriate therapies, and to make predictive testing possible. Mutations identified in a research laboratory must be confirmed in a clinical laboratory to be used clinically. To facilitate the development of clinical genetic testing for a rare disorder, it is useful for a research laboratory to partner with a clinical laboratory. Most clinical molecular assays are developed in research laboratories and must be properly validated. We conclude that the transition of genetic testing for rare diseases from the research laboratory to the clinical laboratory requires a validation process that maintains the quality-control elements necessary for genetic testing but is flexible enough to permit testing to be developed for the benefit of patients and families.

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Inheritance of Frontotemporal Dementia

Cited by 204 publications

References 36 publications

The Early Neuropsychological and Behavioral Characteristics of Frontotemporal Dementia

The Early Neuropsychological and Behavioral Characteristics of Frontotemporal Dementia

Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia

Familial Frontotemporal Dementia: From Gene Discovery to Clinical Molecular Diagnostics

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