Ataxia-telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. Affected children typically develop difficulty walking, problems with balance and hand coordination, involuntary jerking movements (chorea), muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). The movement problems typically cause people to require wheelchair assistance by adolescence. People with this disorder also have slurred speech and trouble moving their eyes to look side-to-side (oculomotor apraxia). Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.
Affected individuals tend to have high amounts of a protein called alpha-fetoprotein (AFP) in their blood. The level of this protein is normally increased in the bloodstream of pregnant women, but it is unknown why individuals with ataxia-telangiectasia have elevated AFP or what effects it has in these individuals.
People with ataxia-telangiectasia often have a weakened immune system, and many develop chronic lung infections. They also have an increased risk of developing cancer, particularly cancer of blood-forming cells (leukemia) and cancer of immune system cells (lymphoma). Affected individuals are very sensitive to the effects of radiation exposure, including medical x-rays. The life expectancy of people with ataxia-telangiectasia varies greatly, but affected individuals typically live into early adulthood.
Ataxia-telangiectasia occurs in 1 in 40,000 to 100,000 people worldwide.
Mutations in the ATM gene cause ataxia-telangiectasia. The ATM gene provides instructions for making a protein that helps control cell division and is involved in DNA repair. This protein plays an important role in the normal development and activity of several body systems, including the nervous system and immune system. The ATM protein assists cells in recognizing damaged or broken DNA strands and coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information.
Mutations in the ATM gene reduce or eliminate the function of the ATM protein. Without this protein, cells become unstable and die. Cells in the part of the brain involved in coordinating movements (the cerebellum) are particularly affected by loss of the ATM protein. The loss of these brain cells causes some of the movement problems characteristic of ataxia-telangiectasia. Mutations in the ATM gene also prevent cells from responding correctly to DNA damage, which allows breaks in DNA strands to accumulate and can lead to the formation of cancerous tumors.
Ataxia-telangiectasia is inherited in an autosomal recessive pattern, which means both copies of the ATM gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
About 1 percent of the United States population carries one mutated copy and one normal copy of the ATM gene in each cell. These individuals are called carriers. Although ATM mutation carriers do not have ataxia-telangiectasia, they are more likely than people without an ATM mutation to develop cancer; female carriers are particularly at risk for developing breast cancer. Carriers of a mutation in the ATM gene also may have an increased risk of heart disease.
5. Other Names for This Condition
- ataxia telangiectasia syndrome
- Louis-Bar syndrome
- telangiectasia, cerebello-oculocutaneous
The entry is from https://medlineplus.gov/genetics/condition/ataxia-telangiectasia
- Biton S, Barzilai A, Shiloh Y. The neurological phenotype ofataxia-telangiectasia: solving a persistent puzzle. DNA Repair (Amst). 2008 Jul1;7(7):1028-38. doi: 10.1016/j.dnarep.2008.03.006.
- Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair(Amst). 2004 Aug-Sep;3(8-9):1187-96. Review.
- Crawford TO, Skolasky RL, Fernandez R, Rosquist KJ, Lederman HM. Survivalprobability in ataxia telangiectasia. Arch Dis Child. 2006 Jul;91(7):610-1.
- de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, Oosterwijk JC,Kleibeuker JH, Schaapveld M, de Vries EG. Genes other than BRCA1 and BRCA2involved in breast cancer susceptibility. J Med Genet. 2002 Apr;39(4):225-42.Review.
- Demuth I, Dutrannoy V, Marques W Jr, Neitzel H, Schindler D, Dimova PS,Chrzanowska KH, Bojinova V, Gregorek H, Graul-Neumann LM, von Moers A, Schulze I,Nicke M, Bora E, Cankaya T, Oláh É, Kiss C, Bessenyei B, Szakszon K,Gruber-Sedlmayr U, Kroisel PM, Sodia S, Goecke TO, Dörk T, Digweed M, Sperling K,de Sá J, Lourenco CM, Varon R. New mutations in the ATM gene and clinical data of25 AT patients. Neurogenetics. 2011 Nov;12(4):273-82. doi:10.1007/s10048-011-0299-0.
- Gatti R, Perlman S. Ataxia-Telangiectasia. 1999 Mar 19 [updated 2016 Oct 27]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK26468/
- Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: geneexpression profiles and sequence variants. Cancer Lett. 2005 Sep28;227(2):105-14.
- McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772-6.Review.
- Perlman S, Becker-Catania S, Gatti RA. Ataxia-telangiectasia: diagnosis andtreatment. Semin Pediatr Neurol. 2003 Sep;10(3):173-82. Review.
- Taylor AM, Byrd PJ. Molecular pathology of ataxia telangiectasia. J ClinPathol. 2005 Oct;58(10):1009-15. Review.
- Verhagen MM, Last JI, Hogervorst FB, Smeets DF, Roeleveld N, Verheijen F,Catsman-Berrevoets CE, Wulffraat NM, Cobben JM, Hiel J, Brunt ER, Peeters EA,Gómez Garcia EB, van der Knaap MS, Lincke CR, Laan LA, Tijssen MA, van Rijn MA,Majoor-Krakauer D, Visser M, van 't Veer LJ, Kleijer WJ, van de Warrenburg BP,Warris A, de Groot IJ, de Groot R, Broeks A, Preijers F, Kremer BH, Weemaes CM,Taylor MA, van Deuren M, Willemsen MA. Presence of ATM protein and residualkinase activity correlates with the phenotype in ataxia-telangiectasia: agenotype-phenotype study. Hum Mutat. 2012 Mar;33(3):561-71. doi:10.1002/humu.22016.