Ataxia–telangiectasia

Ataxia–telangiectasia is a rare inherited disorder caused by pathogenic variants in both copies of ATM. It causes progressive coordination problems, telangiectasias, immune abnormalities, and increased cancer risk.

ATM: ATM is a protein kinase that coordinates cellular responses to DNA double-strand breaks. Biallelic ATM variants cause the disorder by impairing this DNA-damage signaling protein.
Cerebellar ataxia: Impaired coordination caused by dysfunction of the cerebellum or its connections. Progressive cerebellar dysfunction typically produces the earliest movement symptoms in the disorder.
Autosomal recessive inheritance: A pattern in which a condition usually develops when pathogenic variants affect both copies of a gene. Ataxia–telangiectasia generally requires pathogenic ATM variants inherited from both parents.
Ataxia with oculomotor apraxia: A group of inherited disorders featuring progressive ataxia and difficulty initiating voluntary eye movements. It can resemble the neurological presentation but does not characteristically combine ATM-related telangiectasias and cancer risk.
DNA double-strand break: A DNA lesion in which both strands of the double helix are severed near the same site. ATM normally signals when these dangerous breaks occur; defective signaling underlies many cellular vulnerabilities.
Telangiectasia: Persistently dilated small blood vessels visible near the skin or mucosal surface. These vessels commonly appear in the eyes and skin, giving the disorder part of its name.
Cerebellum: A brain structure that helps coordinate movement, balance, and motor learning. Progressive loss of cerebellar neurons drives much of the characteristic incoordination.
Nijmegen breakage syndrome: An inherited DNA-repair disorder marked by microcephaly, immune deficiency, and cancer susceptibility. It shares radiosensitivity and immune problems but typically has distinct growth and facial features.
Non-homologous end joining: A DNA repair pathway that rejoins broken chromosome ends without requiring a matching template. This repair pathway helps developing immune cells assemble receptor genes despite ATM-related damage-response defects.
Immunodeficiency: Reduced ability of the immune system to prevent or control infection. Variable antibody and lymphocyte abnormalities can cause recurrent respiratory infections.

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