Skip to main content Accessibility help
×
Home
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 1
  • Print publication year: 2004
  • Online publication date: July 2009

12 - Ataxia–telangiectasia

Summary

Ataxia–telangiectasia (AT) (MIM 208900) is a neurodegenerative disorder whose onset is marked by slowly progressive ataxia that usually begins in early childhood, telangiectasias (dilated small blood vessels), variable immunodeficiency, and cellular sensitivity to ionizing radiation. AT is an autosomal recessive disorder affecting males and females equally, and estimates of the incidence range from 1 in 40 000 to 1 in 100 000 (Haidar et al., 2000; Brown et al., 2000). The gene frequency may be 1% in the general population (Morrell et al., 1986). The most striking non-neurologic feature of AT is an increased frequency of sinopulmonary infections and a dramatically increased risk for malignancy of the lymphoreticular system, especially leukemia and lymphoma.

Clinical features

Skin and scleral findings

The classic skin findings of AT are telangiectasias most prominently involving the sclerae, the earlobes, and the bridge of the nose (Fig. 12.1). Less common sites include the eyelids, the neck, and the antecubital and popliteal fossae. Telangiectasias typically are not present at birth but develop in early childhood, years after the onset of ataxia, usually between the ages of 3 and 6 years with a mean of 72 months (Harding, 1988). Rarely telangiectasias develop in adulthood or not at all and occasionally they disappear later in life.

Two dermatologic features of AT that are sometimes overlooked are hypertrichosis and scattered gray hairs. Hypertrichosis occurs particularly over the forearms. Progeric changes such as poikiloderma, loss of subcutaneous fat, and sclerosis have also been associated with AT.

REFERENCES
Agamanolis, D. P. & Greenstein, J. I. (1979). Ataxia–telangiectasia. Report of a case with Lewy bodies and vascular abnormalities within cerebral tissue. Journal of Neuropathology and Experimental Neurology 38: 475–489
Angele, S. & Hall, J. (2000). The ATM gene and breast cancer: is it really a risk factor? Mutation Research 462: 167–178
Ataxia–telangiectasia. (2002). Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: 208900: 2/19/02
Aucouturier, P., Bremard-Oury, C., Griscelli, C., Berthier, M. & Preud'homme, J. L. (1987). Serum IgG subclass deficiency in ataxia–telangiectasia. Clinical and Experimental Immunology 68: 392–396
Baloh, R. W., Yee, R. D. & Boder, E.(1978). Eye movements in ataxia–telangiectasia. Neurology 28: 1099–1104
Barbieri, F., Santoro, L., Crisci, C., Massini, R., Russo, E. & Campanella, G. (1986). Is the sensory neuropathy in ataxia–telangiectasia distinguishable from that in Friedreich's ataxia? Morphometric and ultrastructural study of the sural nerve in a case of Louis Bar syndrome. Acta Neuropathologica (Berlin) 69: 213–219
Barbot, C., Coutinho, P., Chorao, R. et al. (2001). Recessive ataxia with ocular apraxia: review of 22 Portuguese patients. Archives of Neurology 58: 201–205
Bodensteiner, J. B., Goldblum, R. M. & Goldman, A. S. (1980). Progressive dystonia masking ataxia in ataxia–telangiectasia. Archives of Neurology 37: 464–465
Brown, K. D., Lataxes, T. A., Shangary, S. et al. (2000). Ionizing radiation exposure results in up-regulation of Ku70 via a p53/ataxia–telangiectasia-mutated protein-dependent mechanism. Journal of Biology and Chemistry 275: 6651–6656
Cabana, M. D., Crawford, T. O., Winkelstein, J. A., Christensen, J. R. & Lederman, H. M. (1998). Consequences of the delayed diagnosis of ataxia–telangiectasia. Pediatrics 102: 98–100
Chessa, L., Piane, M., Prudente, S. et al. (1999). Molecular prenatal diagnosis of ataxia–telangiectasia heterozygosity by direct mutational assays. Prenatal Diagnosis 19: 542–545
Chung, E. O., Bodensteiner, J. B., Noorani, P. A. & Schochet, S. S. (1994). Cerebral white-matter changes suggesting leukodystrophy in ataxia telangiectasia. Journal of Child Neurology 9: 31–35
Cohen, L. E., Tanner, D. J., Schaefer, H. G. & Levis, W. R. (1984). Common and uncommon cutaneous findings in patients with ataxia–telangiectasia. Journal of the American Academy of Dermatology 10: 431–438
Concannon, P. & Gatti, R. A. (1997). Diversity of ATM gene mutations detected in patients with ataxia–telangiectasia. Human Mutation 10: 100–107
Curry, C. J., O'Lague, P., Tsai, J. I. et al. (1989). ATFresno: a phenotype linking ataxia–telangiectasia with the Nijmegen breakage syndrome. American Journal of Human Genetics 45: 270–275
Leon, G. A., Grover, W. D. & Huff, D. S. (1976). Neuropathologic changes in ataxia–telangiectasia. Neurology 26: 947–951
Delia, D., Mizutani, S., Panigone, S. et al. (2000). ATM protein and p53-serine 15 phosphorylation in ataxia–telangiectasia (AT) patients and AT heterozygotes. British Journal of Cancer 82: 1938–1945
Drolet, B. A., Drolet, B., Zvulunov, A., Jacobsen, R., Troy, J. & Esterly, N. B. (1997). Cutaneous granulomas as a presenting sign in ataxia–telangiectasia. Dermatology 194: 273–275
Farina, L., Uggetti, C., Ottolini, A. et al. (1994). ataxia–telangiectasia: MR and CT findings. Journal Computed and Assisted Tomography 18: 724–727
Gatei, M., Shkedy, D., Khanna, K. K. et al. (2001). ataxia–telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid. Oncogene 20: 289–294
Haidar, M. A., Kantarjian, H., Manshouri, T. et al. (2000). ATM gene deletion in patients with adult acute lymphoblastic leukemia. Cancer 88: 1057–1062
Harding, A. E. (1988). The inherited ataxias. Advances in Neurology 48: 37–46
Lewis, R. F., Lederman, H. M. & Crawford, T. O. (1999). Ocular motor abnormalities in ataxia–telangiectasia. Annals of Neurology 46: 287–295
Monaco, S., Nardelli, E., Moretto, G., Cavallaro, T. & Rizzuto, N. (1988). Cytoskeletal pathology in ataxia–telangiectasia. Clinical Neuropathology 7: 44–46
Morrell, D., Cromartie, E. & Swift, M. (1986). Mortality and cancer incidence in 263 patients with ataxia–telangiectasia. Journal of the National Cancer Institute 77: 89–92
Mostofsky, S. H., Kunze, J. C., Cutting, L. E., Lederman, H. M. & Denckla, M. B. (2000). Judgment of duration in individuals with ataxia–telangiectasia. Developmental Neuropsychology 17: 63–74
Nemeth, A. H., Bochukova, E., Dunne, E. et al. (2000). Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia–telangiectasia-like syndrome) is linked to chromosome 9q34. American Journal of Human Genetics 67: 1320–1326
Oka, A. & Takashima, S. (1998). Expression of the ataxia–telangiectasia gene (ATM) product in human cerebellar neurons during development. Neuroscience Letters 252: 195–198
Paller, A. S., Massey, R. B., Curtis, M. A. et al. (1991). Cutaneous granulomatous lesions in patients with ataxia–telangiectasia. Journal of Pediatrics 119: 917–922
Rotman, G. & Shiloh, Y. (1998). ATM: from gene to function. Human Molecular Genetics 7: 1555–1563
Rotman, G. & Shiloh, Y. (1999). ATM: a mediator of multiple responses to genotoxic stress. Oncogene 18: 6135–6144
Spacey, S. D., Gatti, R. A. & Bebb, G. (2000). The molecular basis and clinical management of ataxia–telangiectasia. Canadian Journal of Neurology 27: 184–191
Stankovic, T., Kidd, A. M., Sutcliffe, A. et al. (1998). 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. American Journal of Human Genetics 62: 334–345
Su, Y. & Swift, M. (2000). Mortality rates among carriers of ataxia–telangiectasia mutant alleles. Annals of Internal Medicine 133: 770–778
Taalman, R. D., Hustinx, T. W., Weemaes, C. M. et al. (1989). Further delineation of the Nijmegen breakage syndrome. American Journal of Medical Genetics 32: 425–431