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  • Review Article
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Parkinsonism, movement disorders and genetics in frontotemporal dementia

Nature Reviews Neurology volume 12, pages 175–185 (2016)Cite this article

Subjects

Key Points

  • Atypical parkinsonism is a common presentation in patients with frontotemporal dementia (FTD)

  • Richardson syndrome in FTD is most commonly associated with mutations in the MAPT gene

  • A corticobasal syndrome is most frequently observed in patients who have mutations in the gene that encodes progranulin

  • C9orf72 gene expansions are the most common cause of hereditary motor neuron disease with FTD, and might present in combination with symmetrical parkinsonism

  • Mutations in the VCP, TARDBP and TREM2 genes are rare causes of parkinsonism and motor neuron disease in FTD

  • Stereotypies are common in patients with FTD, and should aid diagnosis

Abstract

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 and TREM2, 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.

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Figure 1: Brain abnormalities that contribute to the pathogenesis of parkinsonism and stereotypies in frontotemporal dementia.
Figure 2: Suggested genetic mutations that should be tested for according to motor presentations.

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Authors and Affiliations

  1. Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, 7200 Cambridge, Suite 9A, MS: BCM 609, Houston, 77030–4202, Texas, USA

    José Fidel Baizabal-Carvallo & Joseph Jankovic

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  1. José Fidel Baizabal-Carvallo
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J.F.B.-C researched data for the article. Both authors made substantial contributions to discussion of the content, wrote the article and reviewed and/or edited the article before submission.

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Correspondence to Joseph Jankovic.

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Baizabal-Carvallo, J., Jankovic, J. Parkinsonism, movement disorders and genetics in frontotemporal dementia. Nat Rev Neurol 12, 175–185 (2016). https://doi.org/10.1038/nrneurol.2016.14

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