Frontotemporal dementia with parkinsonism-17

Frontotemporal dementia with parkinsonism-17 (FTDP-17) is a brain disorder. It is part of a group of conditions, called frontotemporal dementia or frontotemporal degeneration, that are characterized by a loss of nerve cells (neurons) in areas of the brain called the frontal and temporal lobes. Over time, a loss of these cells can affect personality, behavior, language, and movement.

The signs and symptoms of FTDP-17 usually become noticeable in a person's forties or fifties. Most affected people survive 5 to 10 years after the appearance of symptoms, although a few have survived for two decades or more.

Changes in personality and behavior are often early signs of FTDP-17. These changes include a loss of inhibition, inappropriate emotional responses, restlessness, neglect of personal hygiene, and a general loss of interest in activities and events. The disease also leads to deterioration of cognitive functions (dementia), including problems with judgment, planning, and concentration. Some people with FTDP-17 develop psychiatric symptoms, including obsessive-compulsive behaviors, strongly held false beliefs (delusions), and false perceptions (hallucinations). It may become difficult for affected individuals to interact with others in a socially appropriate manner. They increasingly require help with personal care and other activities of daily living.

Many people with FTDP-17 develop problems with speech and language. They may have trouble finding words, confuse one word with another (semantic paraphasias), and repeat words spoken by others (echolalia). Difficulties with speech and language worsen over time, and most affected individuals eventually lose the ability to communicate.

FTDP-17 is also characterized by problems with movement that worsen over time. Many affected individuals develop features of parkinsonism, including tremors, rigidity, and unusually slow movement (bradykinesia). As the disease progresses, most affected individuals become unable to walk. Some people with FTDP-17 also have restricted up-and-down eye movement (vertical gaze palsy) and rapid abnormal movements of both eyes (saccades).

The worldwide prevalence of FTDP-17 is unknown. In the Netherlands, where the disease prevalence has been studied, it is estimated to affect 1 in 1 million people. However, the disorder is likely underdiagnosed, so it may actually be more common than this estimate.

FTDP-17 probably accounts for a small percentage of all cases of frontotemporal dementia.

FTDP-17 is caused by mutations in the MAPT gene. This gene is located on chromosome 17, which is how the disease got its name.

The MAPT gene provides instructions for making a protein called tau. This protein is found throughout the nervous system, including in neurons in the brain. It is involved in assembling and stabilizing microtubules, which are rigid, hollow fibers that make up a cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.

Mutations in the MAPT gene disrupt the normal structure and function of tau. The defective protein forms abnormal clumps within neurons and other brain cells. However, it is unclear what effect these clumps have on cell function and survival. FTDP-17 is characterized by the gradual death of cells in the frontal and temporal lobes of the brain. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. A loss of cells in these brain regions leads to personality changes, speech difficulties, and the other features of FTDP-17.

FTDP-17 is one of several related diseases known as tauopathies, which are characterized by an abnormal buildup of tau in the brain.

Genetic Testing Information

• Genetic Testing Registry: Frontotemporal dementia

Genetic and Rare Diseases Information Center

• Frontotemporal dementia

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• FRONTOTEMPORAL DEMENTIA; FTD

Scientific Articles on PubMed

• PubMed

• Boeve BF, Hutton M. Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Arch Neurol. 2008 Apr;65(4):460-4. doi: 10.1001/archneur.65.4.460. Citation on PubMed or Free article on PubMed Central
• Cohn-Hokke PE, Elting MW, Pijnenburg YA, van Swieten JC. Genetics of dementia: update and guidelines for the clinician. Am J Med Genet B Neuropsychiatr Genet. 2012 Sep;159B(6):628-43. doi: 10.1002/ajmg.b.32080. Epub 2012 Jul 19. Citation on PubMed
• Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JB, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, van Swieten J, Mann D, Lynch T, Heutink P. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998 Jun 18;393(6686):702-5. doi: 10.1038/31508. Citation on PubMed
• Ludolph AC, Kassubek J, Landwehrmeyer BG, Mandelkow E, Mandelkow EM, Burn DJ, Caparros-Lefebvre D, Frey KA, de Yebenes JG, Gasser T, Heutink P, Hoglinger G, Jamrozik Z, Jellinger KA, Kazantsev A, Kretzschmar H, Lang AE, Litvan I, Lucas JJ, McGeer PL, Melquist S, Oertel W, Otto M, Paviour D, Reum T, Saint-Raymond A, Steele JC, Tolnay M, Tumani H, van Swieten JC, Vanier MT, Vonsattel JP, Wagner S, Wszolek ZK; Reisensburg Working Group for Tauopathies With Parkinsonism. Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options. Eur J Neurol. 2009 Mar;16(3):297-309. doi: 10.1111/j.1468-1331.2008.02513.x. Citation on PubMed or Free article on PubMed Central
• Rosso SM, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y, de Jong D, Dooijes D, Kamphorst W, Ravid R, Niermeijer MF, Verheij F, Kremer HP, Scheltens P, van Duijn CM, Heutink P, van Swieten JC. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003 Sep;126(Pt 9):2016-22. doi: 10.1093/brain/awg204. Epub 2003 Jul 22. Citation on PubMed
• Spillantini MG, Van Swieten JC, Goedert M. Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Neurogenetics. 2000 Mar;2(4):193-205. doi: 10.1007/pl00022972. Citation on PubMed
• van Swieten J, Spillantini MG. Hereditary frontotemporal dementia caused by Tau gene mutations. Brain Pathol. 2007 Jan;17(1):63-73. doi: 10.1111/j.1750-3639.2007.00052.x. Citation on PubMed
• van Swieten JC, Stevens M, Rosso SM, Rizzu P, Joosse M, de Koning I, Kamphorst W, Ravid R, Spillantini MG, Niermeijer, Heutink P. Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann Neurol. 1999 Oct;46(4):617-26. doi: 10.1002/1531-8249(199910)46:43.0.co;2-i. Citation on PubMed