Estimating the Inheritance of Frontotemporal Lobar Degeneration in the Italian Population

Article type: Research Article

Authors: Borroni, Barbara^{a; *} | Grassi, Mario^b | Bianchi, Marta^a | Bruni, Amalia Cecilia^c | Maletta, Raffaele Giovanni^c | Anfossi, Maria^c | Pepe, Daniele^b | Cagnin, Annachiara^d | Caffarra, Paolo^e | Cappa, Stefano^f | Clerici, Francesca^g | Daniele, Antonio^h | Frisoni, Giovanni B.ⁱ | Galimberti, Daniela^j | Parnetti, Lucilla^k | Perri, Roberta^l | Rainero, Innocenzo^m | Tremolizzo, Lucioⁿ | Turla, Marinella^o | Zanetti, Orazioⁱ | Padovani, Alessandro^a

Affiliations: [a] Neurology Unit, University of Brescia, Brescia, Italy | [b] Department of Statistics and Epidemiology, University of Pavia, Pavia, Italy | [c] Neurogenetic Research Centre, Lamezia Terme, Azienda Sanitaria Provinciale Catanzaro, Catanzaro, Italy | [d] Department of Neurosciences, University of Padova, Padova, Italy | [e] Department of Neuroscience, University of Parma, Parma, Italy | [f] IRCCS San Raffaele, Universitá Vita e Salute, Milan, Italy | [g] 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 | [h] Neurology Unit, Universitá Cattolica, Rome, Italy | [i] IRCCS Fatebenefratelli, Brescia, Italy | [j] University of Milan, Fondazione CáGranda, IRCCS Ospedale Policlinico, Milan, Italy | [k] Section of Neurology, Centre for Memory Disturbances, University of Perugia, Perugia, Italy | [l] IRCCS Santa Lucia, Rome, Italy | [m] Neurology Unit, University of Torino, Torino, Italy | [n] Department of Neurology, San Gerardo Hospital, Monza and University of Milano-Bicocca, Milano, Italy | [o] Neurology Unit, ValleCamonica Hospital, Esine, Brescia, Italy

Correspondence: [*] Correspondence to: Barbara Borroni, MD, Clinica Neurologica, Universitádegli Studi di Brescia, Piazza Spedali Civili 1, Brescia, Italy. Tel.: +39 0303995632; E-mail: bborroni@inwind.it.

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.

Keywords: Frontotemporal dementia, frontotemporal lobar degeneration, genetics, heritability, inheritance

DOI: 10.3233/JAD-130128

Journal: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 371-376, 2014