Diagnosis and Management in Dementia - Chapter 10: Clinical and pathological phenotypes in dementia: a focus on autosomal dominant frontotemporal dementia

Elsevier, Diagnosis and Management in Dementia, Volume 1, August 2020, Pages 147-164
Innocenzo Rainero, Alessandro Vacca, Elisa Rubino

The term “frontotemporal dementia” (FTD) defines a group of related diseases resulting from progressive degeneration of the temporal and frontal lobes. These areas play a significant role in decision-making, behavioral control, emotion, language, and motor functions. FTD has a strong genetic component, with approximately 10% of cases showing an autosomal dominant transmission of the phenotype (aFTD). Genetic variants in the MAPT, GRN, and C9orf72 genes are the most frequent causes of aFTD. Mutations in a number of other rare genes have been also described. Studies investigating the genotype–phenotype correlations suggest that gene defects may present clinical phenotypes that are partially distinct. MAPT gene mutations generally present an FTD behavioral phenotype, frequently associated with extrapyramidal symptoms. GRN mutations are frequently characterized by psychiatric symptoms, like hallucinations and delusions, associated with language dysfunction and parkinsonism. Finally, patients carrying C9orf72 repeat expansions present with behavioral disturbances, psychotic symptoms, and motor neuron disease. In this chapter, available data regarding the effects of genetic variants on the clinical and pathological characteristics of aFTD will be discussed.