Ataxia-telangiectasia: epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management

Expert Rev Clin Immunol. 2020 Sep;16(9):859-871. doi: 10.1080/1744666X.2020.1810570. Epub 2020 Oct 15.

Abstract

Introduction: Ataxia-telangiectasia (A-T) is a rare autosomal recessive syndrome characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, and cancer predisposition. Mutations cause A-T in the ataxia telangiectasia mutated (ATM) gene encoding a serine/threonine-protein kinase.

Areas covered: The authors reviewed the literature on PubMed, Web of Science, and Scopus databases to collect comprehensive data related to A-T. This review aims to discuss various update aspects of A-T, including epidemiology, pathogenesis, clinical manifestations, diagnosis, prognosis, and management.

Expert opinion: A-T as a congenital disorder has phenotypic heterogeneity, and the severity of symptoms in different patients depends on the severity of mutations. This review provides a comprehensive overview of A-T, although some relevant questions about pathogenesis remain unanswered, probably owing to the phenotypic heterogeneity of this monogenic disorder. The presence of various clinical and immunologic manifestations in A-T indicates that the identification of the role of defective ATM in phenotype can be helpful in the better management and treatment of patients in the future.

Keywords: ATM; Ataxia telangiectasia (A-T); double-strand break repair; oxidative stress; primary immunodeficiency.

Publication types

  • Review

MeSH terms

  • Ataxia Telangiectasia / diagnosis
  • Ataxia Telangiectasia / epidemiology*
  • Ataxia Telangiectasia / therapy
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Humans
  • Mutation / genetics*
  • Oxidative Stress
  • Phenotype
  • Primary Immunodeficiency Diseases / diagnosis
  • Primary Immunodeficiency Diseases / epidemiology*
  • Primary Immunodeficiency Diseases / therapy
  • Risk

Substances

  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins