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Genetics Home Reference: your guide to understanding genetic conditions
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CHMP2B-related frontotemporal dementia

Reviewed August 2010

What is CHMP2B-related frontotemporal dementia?

CHMP2B-related frontotemporal dementia is a progressive brain disorder that affects personality, behavior, and language. The symptoms of this disorder usually become noticeable in a person's fifties or sixties, and affected people survive about 3 to 21 years after the appearance of symptoms.

Changes in personality and behavior are the most common early signs of CHMP2B-related frontotemporal dementia. These changes include inappropriate emotional responses, restlessness, loss of initiative, and neglect of personal hygiene. Affected individuals may overeat sweet foods or place non-food items into their mouths (hyperorality). Additionally, 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 CHMP2B-related frontotemporal dementia develop progressive problems with speech and language (aphasia). They may have trouble speaking, although they can often understand others' speech and written text. Affected individuals may also have difficulty using numbers (dyscalculia). In the later stages of the disease, many completely lose the ability to communicate.

Several years after signs and symptoms first appear, some people with CHMP2B-related frontotemporal dementia develop problems with movement. These movement abnormalities include rigidity, tremors, uncontrolled muscle tensing (dystonia), and involuntary muscle spasms (myoclonus). As the disease progresses, most affected individuals become unable to walk.

How common is CHMP2B-related frontotemporal dementia?

CHMP2B-related frontotemporal dementia has been reported in one large family in Denmark and a few unrelated individuals from other countries. This disease appears to be a rare form of frontotemporal dementia.

What genes are related to CHMP2B-related frontotemporal dementia?

CHMP2B-related frontotemporal dementia results from mutations in the CHMP2B gene. This gene provides instructions for making a protein called charged multivesicular body protein 2B. This protein is active in the brain, where it plays an essential role in transporting proteins that need to be broken down (degraded).

Mutations in the CHMP2B gene lead to the production of an abnormal version of charged multivesicular body protein 2B. Most of the mutations that cause CHMP2B-related frontotemporal dementia result in the production of an abnormal protein that is missing a critical segment at one end. This segment keeps the protein turned off (inactive) when it is not needed. Without this segment, the protein is constantly turned on (active), which disrupts the transport and degradation of other proteins. These abnormalities ultimately lead to the death of nerve cells (neurons) in the brain.

A gradual loss of neurons throughout the brain is characteristic of CHMP2B-related frontotemporal dementia. Many of the features of this disease result from neuronal death 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. It is unclear why the signs and symptoms of this disease are related primarily to the frontal and temporal lobes.

Related Gene(s)

Changes in this gene are associated with CHMP2B-related frontotemporal dementia.

  • CHMP2B

How do people inherit CHMP2B-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 one parent with the condition.

Where can I find information about diagnosis or management of CHMP2B-related frontotemporal dementia?

These resources address the diagnosis or management of CHMP2B-related frontotemporal dementia and may include treatment providers.

  • Family Caregiver Alliance (https://www.caregiver.org/frontotemporal-dementia)
  • Gene Review: Frontotemporal Dementia, Chromosome 3-Linked (http://www.ncbi.nlm.nih.gov/books/NBK1199)
  • Genetic Testing Registry: Frontotemporal Dementia, Chromosome 3-Linked (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1833296)

You might also find information on the diagnosis or management of CHMP2B-related frontotemporal dementia in Educational resources (http://ghr.nlm.nih.gov/condition/chmp2b-related-frontotemporal-dementia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/chmp2b-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 CHMP2B-related frontotemporal dementia?

You may find the following resources about CHMP2B-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 CHMP2B-related frontotemporal dementia?

  • chromosome 3-linked frontotemporal dementia
  • DTM1
  • FTD3
  • FTD-3
  • FTD-CHMP2B

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 CHMP2B-related frontotemporal dementia?

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

What glossary definitions help with understanding CHMP2B-related frontotemporal dementia?

autosomal ; autosomal dominant ; cell ; chromosome ; degradation ; dementia ; dystonia ; gene ; inherited ; involuntary ; myoclonus ; protein ; ubiquitin

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

References

  • Brown J, Ashworth A, Gydesen S, Sorensen A, Rossor M, Hardy J, Collinge J. Familial non-specific dementia maps to chromosome 3. Hum Mol Genet. 1995 Sep;4(9):1625-8. (http://www.ncbi.nlm.nih.gov/pubmed/8541850?dopt=Abstract)
  • Brown J, Gydesen S, Johannsen P, Gade A, Skibinski G, Chakrabarti L, Brun A, Spillantini M, Yancopoulou D, Thusgaard T, Sorensen A, Fisher E, Collinge J; FReJA (Frontotemporal Dementia Research in Jutland Association). Frontotemporal dementia linked to chromosome 3. Dement Geriatr Cogn Disord. 2004;17(4):274-6. (http://www.ncbi.nlm.nih.gov/pubmed/15178935?dopt=Abstract)
  • Brown J. Chromosome 3-linked frontotemporal dementia. Cell Mol Life Sci. 1998 Sep;54(9):925-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9791535?dopt=Abstract)
  • Gene Review: Frontotemporal Dementia, Chromosome 3-Linked (http://www.ncbi.nlm.nih.gov/books/NBK1199)
  • Gydesen S, Brown JM, Brun A, Chakrabarti L, Gade A, Johannsen P, Rossor M, Thusgaard T, Grove A, Yancopoulou D, Spillantini MG, Fisher EM, Collinge J, Sorensen SA. Chromosome 3 linked frontotemporal dementia (FTD-3). Neurology. 2002 Nov 26;59(10):1585-94. (http://www.ncbi.nlm.nih.gov/pubmed/12451202?dopt=Abstract)
  • Holm IE, Englund E, Mackenzie IR, Johannsen P, Isaacs AM. A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3. J Neuropathol Exp Neurol. 2007 Oct;66(10):884-91. (http://www.ncbi.nlm.nih.gov/pubmed/17917582?dopt=Abstract)
  • Lindquist SG, Braedgaard H, Svenstrup K, Isaacs AM, Nielsen JE; FReJA Consortium. Frontotemporal dementia linked to chromosome 3 (FTD-3)--current concepts and the detection of a previously unknown branch of the Danish FTD-3 family. Eur J Neurol. 2008 Jul;15(7):667-70. doi: 10.1111/j.1468-1331.2008.02144.x. Epub 2008 May 15. (http://www.ncbi.nlm.nih.gov/pubmed/18484988?dopt=Abstract)
  • Skibinski G, Parkinson NJ, Brown JM, Chakrabarti L, Lloyd SL, Hummerich H, Nielsen JE, Hodges JR, Spillantini MG, Thusgaard T, Brandner S, Brun A, Rossor MN, Gade A, Johannsen P, Sørensen SA, Gydesen S, Fisher EM, Collinge J. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet. 2005 Aug;37(8):806-8. Epub 2005 Jul 24. (http://www.ncbi.nlm.nih.gov/pubmed/16041373?dopt=Abstract)
  • van der Zee J, Urwin H, Engelborghs S, Bruyland M, Vandenberghe R, Dermaut B, De Pooter T, Peeters K, Santens P, De Deyn PP, Fisher EM, Collinge J, Isaacs AM, Van Broeckhoven C. CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Hum Mol Genet. 2008 Jan 15;17(2):313-22. Epub 2007 Oct 22. (http://www.ncbi.nlm.nih.gov/pubmed/17956895?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: August 2010
Published: October 27, 2014