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Puneet Opal, MD, PhD
Francisco A Bonilla, MD, PhD
Section Editors
Marc C Patterson, MD, FRACP
E Richard Stiehm, MD
Deputy Editor
John F Dashe, MD, PhD


Hereditary ataxia has a variety of causes. One cause is an autosomal recessive disorder associated with defective DNA repair mechanisms: ataxia-telangiectasia (AT; MIM 208900). Patients with AT develop progressive cerebellar ataxia, abnormal eye movements, other neurologic abnormalities, oculocutaneous telangiectasias, and immune deficiency.

This topic will review the genetics and clinical aspects of AT. A closely related disorder, ataxia-telangiectasia-like disorder (ATLD), is also discussed in this review. (See 'Ataxia-telangiectasia-like disorder' below.)

The hereditary ataxias are reviewed elsewhere. (See "Overview of the hereditary ataxias".)


Ataxia-telangiectasia (AT) is an autosomal recessive genetic disorder. The defective gene in AT has been mapped to chromosome 11q22.3, and designated the ATM gene (for AT Mutated) [1,2]. The ATM gene product has one region similar to that of phosphatidylinositol (PI)-3 kinases and another region similar to DNA repair/cell checkpoint genes. It is expressed in all tissues in the body.

ATM is involved in the detection of DNA damage, and plays an important role in cell cycle progression [3]. The latter function is exerted at the transition between the G1 and S phase, when a cell initiates DNA synthesis in preparation for DNA replication. It also functions at the G2 to M transition, during which the cell begins to divide.

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Literature review current through: Nov 2017. | This topic last updated: Jan 03, 2017.
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  1. Gatti RA, Berkel I, Boder E, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature 1988; 336:577.
  2. Savitsky K, Bar-Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995; 268:1749.
  3. Ambrose M, Gatti RA. Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions. Blood 2013; 121:4036.
  4. Khanna KK, Keating KE, Kozlov S, et al. ATM associates with and phosphorylates p53: mapping the region of interaction. Nat Genet 1998; 20:398.
  5. Cortez D, Wang Y, Qin J, Elledge SJ. Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 1999; 286:1162.
  6. Chen J. Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage. Cancer Res 2000; 60:5037.
  7. Swift M, Reitnauer PJ, Morrell D, Chase CL. Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med 1987; 316:1289.
  8. Swift M, Morrell D, Massey RB, Chase CL. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 1991; 325:1831.
  9. Athma P, Rappaport R, Swift M. Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer. Cancer Genet Cytogenet 1996; 92:130.
  10. Thompson D, Duedal S, Kirner J, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 2005; 97:813.
  11. Baskaran R, Wood LD, Whitaker LL, et al. Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 1997; 387:516.
  12. Wu X, Ranganathan V, Weisman DS, et al. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature 2000; 405:477.
  13. Yang DQ, Kastan MB. Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat Cell Biol 2000; 2:893.
  14. Paroni G, Cernotta N, Dello Russo C, et al. PP2A regulates HDAC4 nuclear import. Mol Biol Cell 2008; 19:655.
  15. Li J, Chen J, Ricupero CL, et al. Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia. Nat Med 2012; 18:783.
  16. Kojis TL, Gatti RA, Sparkes RS. The cytogenetics of ataxia telangiectasia. Cancer Genet Cytogenet 1991; 56:143.
  17. Canman CE, Lim DS. The role of ATM in DNA damage responses and cancer. Oncogene 1998; 17:3301.
  18. Suzuki K, Kodama S, Watanabe M. Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation. J Biol Chem 1999; 274:25571.
  19. Barlow C, Hirotsune S, Paylor R, et al. Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 1996; 86:159.
  20. Borghesani PR, Alt FW, Bottaro A, et al. Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci U S A 2000; 97:3336.
  21. Spring K, Ahangari F, Scott SP, et al. Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer. Nat Genet 2002; 32:185.
  22. Eaton JS, Lin ZP, Sartorelli AC, et al. Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. J Clin Invest 2007; 117:2723.
  23. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005; 39:359.
  24. Valentin-Vega YA, Maclean KH, Tait-Mulder J, et al. Mitochondrial dysfunction in ataxia-telangiectasia. Blood 2012; 119:1490.
  25. Paula-Barbosa MM, Ruela C, Tavares MA, et al. Cerebellar cortex ultrastructure in ataxia-telangiectasia. Ann Neurol 1983; 13:297.
  26. Peterson RD, Cooper MD, Good RA. Lymphoid tissue abnormalities associated with ataxia-telangiectasia. Am J Med 1966; 41:342.
  27. Swift M, Morrell D, Cromartie E, et al. The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet 1986; 39:573.
  28. Woods CG, Taylor AM. Ataxia telangiectasia in the British Isles: the clinical and laboratory features of 70 affected individuals. Q J Med 1992; 82:169.
  29. Gatti R. Ataxia-telangiectasia. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK26468/ (Accessed on June 14, 2016).
  30. Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, et al. Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort. Pediatr Res 2016; 79:889.
  31. Moin M, Aghamohammadi A, Kouhi A, et al. Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients. Pediatr Neurol 2007; 37:21.
  32. Stewart E, Prayle AP, Tooke A, et al. Growth and nutrition in children with ataxia telangiectasia. Arch Dis Child 2016; 101:1137.
  33. Crawford TO. Ataxia telangiectasia. Semin Pediatr Neurol 1998; 5:287.
  34. Perlman SL, Boder Deceased E, Sedgewick RP, Gatti RA. Ataxia-telangiectasia. Handb Clin Neurol 2012; 103:307.
  35. Cabana MD, Crawford TO, Winkelstein JA, et al. Consequences of the delayed diagnosis of ataxia-telangiectasia. Pediatrics 1998; 102:98.
  36. Lewis RF, Lederman HM, Crawford TO. Ocular motor abnormalities in ataxia telangiectasia. Ann Neurol 1999; 46:287.
  37. Baloh RW, Yee RD, Boder E. Eye movements in ataxia-telangiectasia. Neurology 1978; 28:1099.
  38. Hoche F, Frankenberg E, Rambow J, et al. Cognitive phenotype in ataxia-telangiectasia. Pediatr Neurol 2014; 51:297.
  39. Vinck A, Verhagen MM, Gerven Mv, et al. Cognitive and speech-language performance in children with ataxia telangiectasia. Dev Neurorehabil 2011; 14:315.
  40. Lefton-Greif MA, Crawford TO, Winkelstein JA, et al. Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia. J Pediatr 2000; 136:225.
  41. Méneret A, Ahmar-Beaugendre Y, Rieunier G, et al. The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia. Neurology 2014; 83:1087.
  42. Kwast O, Ignatowicz R. Progressive peripheral neuron degeneration in ataxia-telangiectasia: an electrophysiological study in children. Dev Med Child Neurol 1990; 32:800.
  43. Taylor MJ, Logan WJ. Multimodal electrophysiological assessment of ataxia telangiectasia. Can J Neurol Sci 1983; 10:261.
  44. Larnaout A, Belal S, Ben Hamida C, et al. Atypical ataxia telangiectasia with early childhood lower motor neuron degeneration: a clinicopathological observation in three siblings. J Neurol 1998; 245:231.
  45. Greenberger S, Berkun Y, Ben-Zeev B, et al. Dermatologic manifestations of ataxia-telangiectasia syndrome. J Am Acad Dermatol 2013; 68:932.
  46. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, et al. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr 2004; 144:505.
  47. Bott L, Lebreton J, Thumerelle C, et al. Lung disease in ataxia-telangiectasia. Acta Paediatr 2007; 96:1021.
  48. McGrath-Morrow SA, Gower WA, Rothblum-Oviatt C, et al. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol 2010; 45:847.
  49. Schroeder SA, Swift M, Sandoval C, Langston C. Interstitial lung disease in patients with ataxia-telangiectasia. Pediatr Pulmonol 2005; 39:537.
  50. Crawford TO, Mandir AS, Lefton-Greif MA, et al. Quantitative neurologic assessment of ataxia-telangiectasia. Neurology 2000; 54:1505.
  51. McGrath-Morrow S, Lefton-Greif M, Rosquist K, et al. Pulmonary function in adolescents with ataxia telangiectasia. Pediatr Pulmonol 2008; 43:59.
  52. Morrell D, Cromartie E, Swift M. Mortality and cancer incidence in 263 patients with ataxia-telangiectasia. J Natl Cancer Inst 1986; 77:89.
  53. Olsen JH, Hahnemann JM, Børresen-Dale AL, et al. Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries. J Natl Cancer Inst 2001; 93:121.
  54. Suarez F, Mahlaoui N, Canioni D, et al. Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol 2015; 33:202.
  55. Morgan JL, Holcomb TM, Morrissey RW. Radiation reaction in ataxia telangiectasia. Am J Dis Child 1968; 116:557.
  56. Iannuzzi CM, Atencio DP, Green S, et al. ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects. Int J Radiat Oncol Biol Phys 2002; 52:606.
  57. Ho AY, Fan G, Atencio DP, et al. Possession of ATM sequence variants as predictor for late normal tissue responses in breast cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 2007; 69:677.
  58. Waldmann TA, McIntire KR. Serum-alpha-fetoprotein levels in patients with ataxia-telangiectasia. Lancet 1972; 2:1112.
  59. Waldmann TA, Broder S, Goldman CK, et al. Disorders of B cells and helper T cells in the pathogenesis of the immunoglobulin deficiency of patients with ataxia telangiectasia. J Clin Invest 1983; 71:282.
  60. Rivat-Peran L, Buriot D, Salier JP, et al. Immunoglobulins in ataxia-telangiectasia: evidence for IgG4 and IgA2 subclass deficiencies. Clin Immunol Immunopathol 1981; 20:99.
  61. Roifman CM, Gelfand EW. Heterogeneity of the immunological deficiency in ataxia-telangiectasia: absence of a clinical-pathological correlation. Kroc Found Ser 1985; 19:273.
  62. Sanal O, Ersoy F, Yel L, et al. Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia-telangiectasia. J Clin Immunol 1999; 19:326.
  63. Sadighi Akha AA, Humphrey RL, Winkelstein JA, et al. Oligo-/monoclonal gammopathy and hypergammaglobulinemia in ataxia-telangiectasia. A study of 90 patients. Medicine (Baltimore) 1999; 78:370.
  64. Fiorilli M, Businco L, Pandolfi F, et al. Heterogeneity of immunological abnormalities in ataxia-telangiectasia. J Clin Immunol 1983; 3:135.
  65. Giovannetti A, Mazzetta F, Caprini E, et al. Skewed T-cell receptor repertoire, decreased thymic output, and predominance of terminally differentiated T cells in ataxia telangiectasia. Blood 2002; 100:4082.
  66. Cawley LP, Schenken JR. Monoclonal hypergammaglobulinemia of the gamma M type in a nine-year-old girl with ataxia-telangiectasia. Am J Clin Pathol 1970; 54:790.
  67. Taylor AM, Oxford JM, Metcalfe JA. Spontaneous cytogenetic abnormalities in lymphocytes from thirteen patients with ataxia telangiectasia. Int J Cancer 1981; 27:311.
  68. McConville CM, Stankovic T, Byrd PJ, et al. Mutations associated with variant phenotypes in ataxia-telangiectasia. Am J Hum Genet 1996; 59:320.
  69. Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst) 2004; 3:1187.
  70. Dörk T, Bendix-Waltes R, Wegner RD, Stumm M. Slow progression of ataxia-telangiectasia with double missense and in frame splice mutations. Am J Med Genet A 2004; 126A:272.
  71. Alterman N, Fattal-Valevski A, Moyal L, et al. Ataxia-telangiectasia: mild neurological presentation despite null ATM mutation and severe cellular phenotype. Am J Med Genet A 2007; 143A:1827.
  72. Verhagen MM, Abdo WF, Willemsen MA, et al. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology 2009; 73:430.
  73. Saunders-Pullman R, Raymond D, Stoessl AJ, et al. Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites. Neurology 2012; 78:649.
  74. Charlesworth G, Mohire MD, Schneider SA, et al. Ataxia telangiectasia presenting as dopa-responsive cervical dystonia. Neurology 2013; 81:1148.
  75. Su Y, Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med 2000; 133:770.
  76. Olsen JH, Hahnemann JM, Børresen-Dale AL, et al. Breast and other cancers in 1445 blood relatives of 75 Nordic patients with ataxia telangiectasia. Br J Cancer 2005; 93:260.
  77. Renwick A, Thompson D, Seal S, et al. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 2006; 38:873.
  78. Concannon P. ATM heterozygosity and cancer risk. Nat Genet 2002; 32:89.
  79. FitzGerald MG, Bean JM, Hegde SR, et al. Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet 1997; 15:307.
  80. Dörk T, Bendix R, Bremer M, et al. Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients. Cancer Res 2001; 61:7608.
  81. Gatti RA, Tward A, Concannon P. Cancer risk in ATM heterozygotes: a model of phenotypic and mechanistic differences between missense and truncating mutations. Mol Genet Metab 1999; 68:419.
  82. Chenevix-Trench G, Spurdle AB, Gatei M, et al. Dominant negative ATM mutations in breast cancer families. J Natl Cancer Inst 2002; 94:205.
  83. Teraoka SN, Malone KE, Doody DR, et al. Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history. Cancer 2001; 92:479.
  84. Stankovic T, Kidd AM, Sutcliffe A, et al. ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. Am J Hum Genet 1998; 62:334.
  85. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 1999; 93:190.
  86. Wu JT, Book L, Sudar K. Serum alpha fetoprotein (AFP) levels in normal infants. Pediatr Res 1981; 15:50.
  87. Butch AW, Chun HH, Nahas SA, Gatti RA. Immunoassay to measure ataxia-telangiectasia mutated protein in cellular lysates. Clin Chem 2004; 50:2302.
  88. Chun HH, Sun X, Nahas SA, et al. Improved diagnostic testing for ataxia-telangiectasia by immunoblotting of nuclear lysates for ATM protein expression. Mol Genet Metab 2003; 80:437.
  89. Maserati E, Ottolini A, Veggiotti P, et al. Ataxia-without-telangiectasia in two sisters with rearrangements of chromosomes 7 and 14. Clin Genet 1988; 34:283.
  90. Aicardi J, Barbosa C, Andermann E, et al. Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia. Ann Neurol 1988; 24:497.
  91. Moreira MC, Barbot C, Tachi N, et al. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet 2001; 29:189.
  92. Date H, Onodera O, Tanaka H, et al. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet 2001; 29:184.
  93. Shimazaki H, Takiyama Y, Sakoe K, et al. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations. Neurology 2002; 59:590.
  94. Criscuolo C, Mancini P, Saccà F, et al. Ataxia with oculomotor apraxia type 1 in Southern Italy: late onset and variable phenotype. Neurology 2004; 63:2173.
  95. Musumeci O, Naini A, Slonim AE, et al. Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 2001; 56:849.
  96. Lamperti C, Naini A, Hirano M, et al. Cerebellar ataxia and coenzyme Q10 deficiency. Neurology 2003; 60:1206.
  97. Quinzii CM, Kattah AG, Naini A, et al. Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 2005; 64:539.
  98. Le Ber I, Dubourg O, Benoist JF, et al. Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1. Neurology 2007; 68:295.
  99. Németh AH, Bochukova E, Dunne E, et al. Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome) is linked to chromosome 9q34. Am J Hum Genet 2000; 67:1320.
  100. Moreira MC, Klur S, Watanabe M, et al. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet 2004; 36:225.
  101. Duquette A, Roddier K, McNabb-Baltar J, et al. Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. Ann Neurol 2005; 57:408.
  102. Anheim M, Fleury MC, Franques J, et al. Clinical and molecular findings of ataxia with oculomotor apraxia type 2 in 4 families. Arch Neurol 2008; 65:958.
  103. Anheim M, Monga B, Fleury M, et al. Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain 2009; 132:2688.
  104. Stewart GS, Maser RS, Stankovic T, et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 1999; 99:577.
  105. Hernandez D, McConville CM, Stacey M, et al. A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 11q22-23. J Med Genet 1993; 30:135.
  106. Klein C, Wenning GK, Quinn NP, Marsden CD. Ataxia without telangiectasia masquerading as benign hereditary chorea. Mov Disord 1996; 11:217.
  107. Crawford TO, Skolasky RL, Fernandez R, et al. Survival probability in ataxia telangiectasia. Arch Dis Child 2006; 91:610.
  108. Zannolli R, Buoni S, Betti G, et al. A randomized trial of oral betamethasone to reduce ataxia symptoms in ataxia telangiectasia. Mov Disord 2012; 27:1312.
  109. Broccoletti T, Del Giudice E, Cirillo E, et al. Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia. Eur J Neurol 2011; 18:564.
  110. Montella S, Mollica C, Finocchi A, et al. Non invasive assessment of lung disease in ataxia telangiectasia by high-field magnetic resonance imaging. J Clin Immunol 2013; 33:1185.
  111. Gatti R. Ataxia-telangiectasia. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK26468/ (Accessed on September 10, 2014).
  112. Byrd PJ, Srinivasan V, Last JI, et al. Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia. Br J Cancer 2012; 106:262.
  113. DeWire MD, Beltran C, Boop FA, et al. Radiation therapy and adjuvant chemotherapy in a patient with a malignant glioneuronal tumor and underlying ataxia telangiectasia: a case report and review of the literature. J Clin Oncol 2013; 31:e12.
  114. Seidemann K, Henze G, Beck JD, et al. Non-Hodgkin's lymphoma in pediatric patients with chromosomal breakage syndromes (AT and NBS): experience from the BFM trials. Ann Oncol 2000; 11 Suppl 1:141.
  115. Ussowicz M, Musiał J, Duszeńko E, et al. Long-term survival after allogeneic-matched sibling PBSC transplantation with conditioning consisting of low-dose busilvex and fludarabine in a 3-year-old boy with ataxia-telangiectasia syndrome and ALL. Bone Marrow Transplant 2013; 48:740.
  116. Ghosh S, Schuster FR, Binder V, et al. Fatal outcome despite full lympho-hematopoietic reconstitution after allogeneic stem cell transplantation in atypical ataxia telangiectasia. J Clin Immunol 2012; 32:438.
  117. Nissenkorn A, Hassin-Baer S, Lerman SF, et al. Movement disorder in ataxia-telangiectasia: treatment with amantadine sulfate. J Child Neurol 2013; 28:155.