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GRN-related frontotemporal lobar degeneration is a progressive brain disorder that can affect behavior, language, and movement.

genetic conditions
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Update Time: 23 Dec 2020

1. Introduction

The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people typically survive 7 to 13 years after the appearance of symptoms. However, symptoms can begin as early as a person's thirties or as late as a person's eighties. 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 lobar degeneration. 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 lobar degeneration 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 (mutism). People with this condition also experience a decline in intellectual function (dementia).

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

2. Frequency

The prevalence of GRN-related frontotemporal lobar degeneration varies worldwide. It affects an estimated 3 to 15 per 100,000 people aged 45 to 64.

3. Causes

GRN-related frontotemporal lobar degeneration results from mutations (pathogenic variants) in the GRN gene. This gene provides instructions for making a protein called progranulin. Progranulin is active in many different tissues in the body, where it helps control the growth, division, and survival of cells. Progranulin'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 progranulin from being produced from one copy of the gene in each cell. As a result, cells make only half the usual amount of progranulin. It is unclear how a shortage of this protein leads to the features of GRN-related frontotemporal lobar degeneration. However, studies have shown that the disorder is characterized by the buildup of a protein called TAR DNA-binding protein 43 (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 progranulin, are related to a buildup of TDP-43 in the brain.

The features of GRN-related frontotemporal lobar degeneration 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 lobar degeneration.

4. Inheritance

GRN-related frontotemporal lobar degeneration has a pattern of inheritance known as incomplete autosomal dominance. This means having one copy of the altered gene generally results in milder signs and symptoms than having both copies of the altered gene. People with a mutation in one copy of the GRN gene in each cell (heterozygotes) have some functional progranulin protein and develop GRN-related frontotemporal lobar degeneration. Usually, people with a mutation in both copies of the GRN gene in each cell (homozygotes) do not produce any functional progranulin protein. These individuals have the signs and symptoms of another condition called CLN11 disease, in which movement and neurological problems begin in adolescence or early adulthood. However, some people with two GRN gene mutations that allow the production of some functional progranulin protein have GRN-related frontotemporal lobar degeneration.

In most cases of GRN-related frontotemporal lobar degeneration, an affected person has a parent and other family members with the condition.

5. Other Names for This Condition

  • frontotemporal lobar degeneration

  • FTD-GRN

  • FTD-PGRN

  • FTDP-17 GRN

  • FTDU-17

  • FTLD

  • FTLD with TDP-43 pathology

  • FTLD-TDP

  • GRN-related frontotemporal dementia

  • HDDD1

  • HDDD2

  • hereditary dysphasic disinhibition dementia

References

  1. Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick T, Brushaber D, Dheel C,Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford N, Jack CR Jr, Jones D, Knopman D, Kremers WK, Lapid M, Rademakers R, Ramos EM,Syrjanen J, Boxer AL, Rosen H, Wszolek ZK, Kantarci K. Trajectory of lobaratrophy in asymptomatic and symptomatic GRN mutation carriers: a longitudinal MRIstudy. Neurobiol Aging. 2020 Apr;88:42-50. doi:10.1016/j.neurobiolaging.2019.12.004.
  2. Hsiung GYR, Feldman HH. GRN Frontotemporal Dementia. 2007 Sep 7 [updated 2020 Feb 6]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1371/
  3. 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 andgenetic study. Brain. 2008 Mar;131(Pt 3):732-46. doi: 10.1093/brain/awn012.
  4. Rabins PV, Rovner BW, Rummans T, Schneider LS, Tariot PN. Guideline Watch(October 2014): Practice Guideline for the Treatment of Patients With Alzheimer'sDisease and Other Dementias. Focus (Am Psychiatr Publ). 2017 Jan;15(1):110-128.doi: 10.1176/appi.focus.15106.
  5. Ramos EM, Dokuru DR, Van Berlo V, Wojta K, Wang Q, Huang AY, Deverasetty S,Qin Y, van Blitterswijk M, Jackson J, Appleby B, Bordelon Y, Brannelly P,Brushaber DE, Dickerson B, Dickinson S, Domoto-Reilly K, Faber K, Fields J, Fong J, Foroud T, Forsberg LK, Gavrilova R, Ghoshal N, Goldman J, Graff-Radford J,Graff-Radford N, Grant I, Grossman M, Heuer HW, Hsiung GR, Huey E, Irwin D,Kantarci K, Karydas A, Kaufer D, Kerwin D, Knopman D, Kornak J, Kramer JH,Kremers W, Kukull W, Litvan I, Ljubenkov P, Lungu C, Mackenzie I, Mendez MF,Miller BL, Onyike C, Pantelyat A, Pearlman R, Petrucelli L, Potter M, Rankin KP, Rascovsky K, Roberson ED, Rogalski E, Shaw L, Syrjanen J, Tartaglia MC, Tatton N,Taylor J, Toga A, Trojanowski JQ, Weintraub S, Wong B, Wszolek Z, Rademakers R,Boeve BF, Rosen HJ, Boxer AL; ARTFL/LEFFTDS consortium, Coppola G. Geneticscreening of a large series of North American sporadic and familialfrontotemporal dementia cases. Alzheimers Dement. 2020 Jan;16(1):118-130. doi:10.1002/alz.12011.
  6. Staffaroni AM, Bajorek L, Casaletto KB, Cobigo Y, Goh SM, Wolf A, Heuer HW,Elahi FM, Ljubenkov PA, Dever R, Kornak J, Appleby B, Bove J, Bordelon Y,Brannelly P, Brushaber D, Caso C, Coppola G, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reilly K, Faber K, Ferrall J, Fields JA, Fishman A, Fong J,Foroud T, Forsberg LK, Gavrilova R, Gearhart D, Ghazanfari B, Ghoshal N, Goldman J, Graff-Radford J, Graff-Radford N, Grant I, Grossman M, Haley D, Hsiung GY,Huey ED, Irwin DJ, Jones DT, Jones L, Kantarci K, Karydas A, Kaufer DI, KerwinDR, Knopman DS, Kraft R, Kremers WK, Kukull WA, Litvan I, Lucente D, Lungu C,Mackenzie IR, Maldonado M, Manoochehri M, McGinnis SM, McKinley E, Mendez MF,Miller BL, Multani N, Onyike C, Padmanabhan J, Pantelyat A, Pearlman R,Petrucelli L, Potter M, Rademakers R, Ramos EM, Rankin KP, Rascovsky K, Roberson ED, Rogalski E, Sengdy P, Shaw LM, Syrjanen J, Tartaglia MC, Tatton N, Taylor J, Toga A, Trojanowski JQ, Weintraub S, Wang P, Wong B, Wszolek Z, Boxer AL, BoeveBF, Kramer JH, Rosen HJ; ARTFL/LEFFTDS consortium. Assessment of executivefunction declines in presymptomatic and mildly symptomatic familialfrontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint.Alzheimers Dement. 2020 Jan;16(1):11-21. doi: 10.1016/j.jalz.2019.01.012.
  7. 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 pathologiccharacteristics of patients with frontotemporal dementia and progranulinmutations. Arch Neurol. 2007 Aug;64(8):1148-53.
  8. van Swieten JC, Heutink P. Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia. LancetNeurol. 2008 Oct;7(10):965-74. doi: 10.1016/S1474-4422(08)70194-7.
  9. 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 ofmutations in progranulin: a collaborative study screening 545 cases ofneurodegeneration. Arch Neurol. 2010 Feb;67(2):161-70. doi:10.1001/archneurol.2009.328.
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View Times: 66
Entry Collection: MedlinePlus
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Update Time: 23 Dec 2020
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    Xu, C. GRN-Related Frontotemporal Lobar Degeneration. Encyclopedia. Available online: https://encyclopedia.pub/entry/3959 (accessed on 03 October 2022).
    Xu C. GRN-Related Frontotemporal Lobar Degeneration. Encyclopedia. Available at: https://encyclopedia.pub/entry/3959. Accessed October 03, 2022.
    Xu, Camila. "GRN-Related Frontotemporal Lobar Degeneration," Encyclopedia, https://encyclopedia.pub/entry/3959 (accessed October 03, 2022).
    Xu, C. (2020, December 23). GRN-Related Frontotemporal Lobar Degeneration. In Encyclopedia. https://encyclopedia.pub/entry/3959
    Xu, Camila. ''GRN-Related Frontotemporal Lobar Degeneration.'' Encyclopedia. Web. 23 December, 2020.
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