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GRN-related frontotemporal dementia

Reviewed September 2010

What is GRN-related frontotemporal dementia?

GRN-related frontotemporal dementia is a progressive brain disorder that can affect behavior, language, and movement. The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people typically survive 6 to 7 years after the appearance of symptoms. However, the features of this condition vary significantly, even among affected members of the same family.

Behavioral changes are the most common early signs of GRN-related frontotemporal dementia. These include marked changes in personality, judgment, and insight. It may become difficult for affected individuals to interact with others in a socially appropriate manner. Affected people may also become easily distracted and unable to complete tasks. They increasingly require help with personal care and other activities of daily living.

Many people with GRN-related frontotemporal dementia develop progressive problems with speech and language (aphasia). Affected individuals may have trouble speaking, remembering words and names (dysnomia), and understanding speech. Over time, they may completely lose the ability to communicate.

Some people with GRN-related frontotemporal dementia also develop movement disorders, such as parkinsonism and corticobasal syndrome. The signs and symptoms of these disorders include tremors, rigidity, unusually slow movement (bradykinesia), involuntary muscle spasms (myoclonus), uncontrolled muscle tensing (dystonia), and an inability to carry out purposeful movements (apraxia).

How common is GRN-related frontotemporal dementia?

GRN-related frontotemporal dementia affects an estimated 3 to 15 per 100,000 people aged 45 to 64. This condition accounts for 5 to 10 percent of all cases of frontotemporal dementia.

What genes are related to GRN-related frontotemporal dementia?

GRN-related frontotemporal dementia results from mutations in the GRN gene. This gene provides instructions for making a protein called granulin (also known as progranulin). Granulin is active in many different tissues in the body, where it helps control the growth, division, and survival of cells. Granulin's function in the brain is not well understood, although it appears to play an important role in the survival of nerve cells (neurons).

Most mutations in the GRN gene prevent any granulin from being produced from one copy of the gene in each cell. As a result, cells make only half the usual amount of granulin. It is unclear how a shortage of this protein leads to the features of GRN-related frontotemporal dementia. However, studies have shown that the disorder is characterized by the buildup of a protein called TAR DNA-binding protein (TDP-43) in certain brain cells. The TDP-43 protein forms clumps (aggregates) that may interfere with cell functions and ultimately lead to cell death. Researchers are working to determine how mutations in the GRN gene, and the resulting loss of granulin, are related to a buildup of TDP-43 in the brain.

The features of GRN-related frontotemporal dementia result from the gradual loss of neurons in regions near the front of the brain called the frontal and temporal lobes. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. The death of neurons in these areas causes problems with many critical brain functions. However, it is unclear why the loss of neurons occurs in the frontal and temporal lobes more often than other brain regions in people with GRN-related frontotemporal dementia.

Related Gene(s)

Changes in this gene are associated with GRN-related frontotemporal dementia.

  • GRN

How do people inherit GRN-related frontotemporal dementia?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has a parent and other family members with the condition.

Where can I find information about diagnosis or management of GRN-related frontotemporal dementia?

These resources address the diagnosis or management of GRN-related frontotemporal dementia and may include treatment providers.

  • Family Caregiver Alliance (https://www.caregiver.org/frontotemporal-dementia)
  • Gene Review: GRN-Related Frontotemporal Dementia (http://www.ncbi.nlm.nih.gov/books/NBK1371/)
  • Genetic Testing Registry: Frontotemporal dementia, ubiquitin-positive (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1843792)

You might also find information on the diagnosis or management of GRN-related frontotemporal dementia in Educational resources (http://www.ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/grn-related-frontotemporal-dementia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about GRN-related frontotemporal dementia?

You may find the following resources about GRN-related frontotemporal dementia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for GRN-related frontotemporal dementia?

  • frontotemporal lobar degeneration
  • FTD-GRN
  • FTDP-17 GRN
  • FTD-PGRN
  • FTDU-17
  • FTLD
  • FTLD-TDP
  • FTLD with TDP-43 pathology
  • HDDD1
  • HDDD2
  • hereditary dysphasic disinhibition dementia

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about GRN-related frontotemporal dementia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding GRN-related frontotemporal dementia?

apraxia ; autosomal ; autosomal dominant ; bradykinesia ; cell ; dementia ; DNA ; dystonia ; gene ; hereditary ; inherited ; involuntary ; myoclonus ; parkinsonism ; protein ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006 Aug 24;442(7105):916-9. Epub 2006 Jul 16. (http://www.ncbi.nlm.nih.gov/pubmed/16862116?dopt=Abstract)
  • Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, Van Broeckhoven C. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006 Aug 24;442(7105):920-4. Epub 2006 Jul 16. (http://www.ncbi.nlm.nih.gov/pubmed/16862115?dopt=Abstract)
  • Gene Review: GRN-Related Frontotemporal Dementia (http://www.ncbi.nlm.nih.gov/books/NBK1371/)
  • Le Ber I, Camuzat A, Hannequin D, Pasquier F, Guedj E, Rovelet-Lecrux A, Hahn-Barma V, van der Zee J, Clot F, Bakchine S, Puel M, Ghanim M, Lacomblez L, Mikol J, Deramecourt V, Lejeune P, de la Sayette V, Belliard S, Vercelletto M, Meyrignac C, Van Broeckhoven C, Lambert JC, Verpillat P, Campion D, Habert MO, Dubois B, Brice A; French research network on FTD/FTD-MND. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. Brain. 2008 Mar;131(Pt 3):732-46. doi: 10.1093/brain/awn012. Epub 2008 Feb 1. (http://www.ncbi.nlm.nih.gov/pubmed/18245784?dopt=Abstract)
  • Mackenzie IR. The neuropathology and clinical phenotype of FTD with progranulin mutations. Acta Neuropathol. 2007 Jul;114(1):49-54. Epub 2007 Apr 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17458552?dopt=Abstract)
  • Van Deerlin VM, Wood EM, Moore P, Yuan W, Forman MS, Clark CM, Neumann M, Kwong LK, Trojanowski JQ, Lee VM, Grossman M. Clinical, genetic, and pathologic characteristics of patients with frontotemporal dementia and progranulin mutations. Arch Neurol. 2007 Aug;64(8):1148-53. (http://www.ncbi.nlm.nih.gov/pubmed/17698705?dopt=Abstract)
  • van Swieten JC, Heutink P. Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia. Lancet Neurol. 2008 Oct;7(10):965-74. doi: 10.1016/S1474-4422(08)70194-7. Epub 2008 Sep 2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18771956?dopt=Abstract)
  • Yu CE, Bird TD, Bekris LM, Montine TJ, Leverenz JB, Steinbart E, Galloway NM, Feldman H, Woltjer R, Miller CA, Wood EM, Grossman M, McCluskey L, Clark CM, Neumann M, Danek A, Galasko DR, Arnold SE, Chen-Plotkin A, Karydas A, Miller BL, Trojanowski JQ, Lee VM, Schellenberg GD, Van Deerlin VM. The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration. Arch Neurol. 2010 Feb;67(2):161-70. doi: 10.1001/archneurol.2009.328. (http://www.ncbi.nlm.nih.gov/pubmed/20142524?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2010
Published: September 1, 2014