title: Estimating the inheritance of frontotemporal lobar degeneration in the Italian population.
abstract: Frontotemporal dementia (FTD) has a strong genetic basis, with familial forms occurring in 30-50% of cases. Causative genes have been identified, with an autosomal dominant pattern of inheritance. Notwithstanding, in a number of cases with positive family history no pathogenetic mutation has been reported, and the role of genetics in sporadic cases is still unclear. In the present study, we aim to estimate the genetic contribution to FTD using concordance among parent-offspring pairs. Heritability of early-onset (EO, <65 years) and late-onset (LO, ≥65 years) FTD was estimated by examining the concordance between parents and offspring. Probands with at least one parent whose dementia status was known were recruited from 15 Italian centers, and the presence or absence of dementia was considered in siblings. Different prevalence estimates, as available by literature data, were tested. A total of 260 probands and 1619 family members were considered in this study. We found that parent-offspring concordance in FTD was 6.25%, resulting in hereditability of 98.5% (95% confidence interval (CI): 85.0%-100.0%). Equal heritability for both sexes regardless of parental gender was reported. EO-FTD showed hereditability of 86.3% (95% CI: 77.0%-95.0%) and LO-FTD of 75.7% (95% CI: 65.0%-86.0%). Estimating the contribution of genetics in FTD may help in driving future genetic studies to identify new pathogenetic determinants. We suggest that in most of the cases FTD is a genetic-based disease, even in the elderly. Different inheritance modality might be considered in future work, beyond autosomal dominant disease.
authors.affiliation: Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.affiliation: Department of Statistics and Epidemiology, University of Pavia, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.affiliation: Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Neurogenetic Research Centre, Lamezia Terme, Azienda Sanitaria Provinciale Catanzaro, Catanzaro, Italy.
authors.forename: Amalia Cecilia
authors.initials: AC
authors.lastname: Bruni
authors.affiliation: Neurogenetic Research Centre, Lamezia Terme, Azienda Sanitaria Provinciale Catanzaro, Catanzaro, Italy.
authors.forename: Raffaele Giovanni
authors.initials: RG
authors.lastname: Maletta
authors.affiliation: Neurogenetic Research Centre, Lamezia Terme, Azienda Sanitaria Provinciale Catanzaro, Catanzaro, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Anfossi
authors.affiliation: Department of Statistics and Epidemiology, University of Pavia, Pavia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pepe
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Annachiara
authors.initials: A
authors.lastname: Cagnin
authors.affiliation: Department of Neuroscience, University of Parma, Parma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Caffarra
authors.affiliation: IRCCS San Raffaele, Universitá Vita e Salute, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cappa
authors.affiliation: Center for Research and Treatment of Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Biomedical and Clinical Sciences, "Luigi Sacco" Hospital, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Clerici
authors.affiliation: Neurology Unit, Universitá Cattolica, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Daniele
authors.affiliation: IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: University of Milan, Fondazione CáGranda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.affiliation: IRCCS Santa Lucia, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Perri
authors.affiliation: Neurology Unit, University of Torino, Torino, Italy.
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
authors.affiliation: Department of Neurology, San Gerardo Hospital, Monza and University of Milano-Bicocca, Milano, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Tremolizzo
authors.affiliation: Neurology Unit, ValleCamonica Hospital, Esine, Brescia, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Turla
authors.affiliation: IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Zanetti
authors.affiliation: Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D017668:Age of Onset; D000368:Aged; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010290:Parents; D012042:Registries; D012737:Sex Factors
keywords: Frontotemporal dementia; frontotemporal lobar degeneration; genetics; heritability; inheritance