Frontotemporal Lobar Degeneration: Genetics and Clinical Phenotypes

Abstract

Frontotemporal lobar degeneration (FTLD) is the most frequent dementia in the presenile population. It presents with different syndromes, including behavioral variant frontotemporal dementia (bvFTD), primary nonfluent aphasia (PNFA), semantic dementia (SD), and logopenic aphasia. In 2011, new diagnostic criteria bvFTD, which include the use of biomarkers, have been published. According to them, bvFTD can be classified into “possible” (clinical features only), “probable” (inclusion of imaging biomarkers), and “definite” (in the presence of a known causal mutation or at autopsy). Motor neuron degeneration often co-occurs with FTLD. In the last few years, different autosomal dominant mutations have been demonstrated to be the cause of the familial aggregation frequently reported in FTLD. Major causal genes so far discovered include microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame (C9ORF)72. Mutations in MAPT are generally associated with early onset and with the bvFTD phenotype, whereas mutations in GRN and C9ORF72 are associated with high clinical heterogeneity and age at disease onset. In addition, other genes are linked to rare cases of familial FTLD.