Parkinsonism, movement disorders and genetics in frontotemporal dementia

Frontotemporal dementia (FTD) refers to a group of clinically and genetically heterogeneous neurodegenerative disorders that are a common cause of adult-onset behavioural and cognitive impairment. FTD often presents in combination with various hyperkinetic or hypokinetic movement disorders, and evidence suggests that various genetic mutations underlie these different presentations. Here, we review the known syndromatic–genetic correlations in FTD. Although no direct genotype–phenotype correlations have been identified, mutations in multiple genes have been associated with various presentations. Mutations in the genes that encode microtubule-associated protein tau (MAPT) and progranulin (PGRN) can manifest as symmetrical parkinsonism, including the phenotypes of Richardson syndrome and corticobasal syndrome (CBS). Expansions in the C9orf72 gene are most frequently associated with familial FTD, typically combined with motor neuron disease, but other manifestations, such as symmetrical parkinsonism, CBS and multiple system atrophy-like presentations, have been described in patients with these mutations. Less common gene mutations, such as those in TARDBP, CHMP2B, VCP, FUS andTREM2, can also present as atypical parkinsonism. The most common hyperkinetic movement disorders in FTD are motor and vocal stereotypies, which have been observed in up to 78% of patients with autopsy-proven FTD. Other hyperkinetic movements, such as chorea, orofacial dyskinesias, myoclonus and dystonia, are also observed in some patients with FTD.

Nature Reviews Neurology 2016