Ataxia Telangiectasia Clinical Features and Genetic Variability

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterised by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency and heightened cancer susceptibility. Neurological decline typically emerges in early childhood with gait instability, dysarthria and oculomotor apraxia. Telangiectasia appears later and may affect conjunctival and cutaneous capillaries. Immunological defects arise from impaired B- and T-cell maturation and class switch recombination, leading to recurrent sinopulmonary infections. DNA double-strand break repair failure underpins chromosomal instability, radiation sensitivity and oncogenesis, most often lymphoid malignancies. Genetically, A-T results from biallelic pathogenic variants in the ATM gene encoding a serine-threonine kinase crucial for DNA damage response. Truncating mutations usually cause classical A-T, whereas hypomorphic or missense mutations may retain residual kinase activity and manifest as milder, variant phenotypes with later onset, predominant extrapyramidal features or attenuated immunodeficiency. Genotype-phenotype correlations guide prognosis, surveillance strategies and genetic counselling for affected families worldwide.

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Ataxia Telangiectasia Clinical Features and Genetic Variability publication trend

The graph below shows the total number of articles in ataxia telangiectasia clinical features and genetic variability across all publications each year (not limited to Nature Index journals).

Technical terms

ATM gene: Gene encoding a protein kinase activated by DNA double-strand breaks to orchestrate repair and cell cycle checkpoints.

Ataxia: Impaired coordination of voluntary movements due to cerebellar dysfunction.

Telangiectasia: Small dilated blood vessels visible beneath the skin or mucous membranes.

Class switch recombination: Mechanism by which B-cells change immunoglobulin isotype to diversify antibody effector functions.

Missense mutation: Single nucleotide substitution resulting in an amino acid change in the encoded protein.

Kinase activity: Enzymatic function of transferring phosphate groups to protein substrates, regulating cellular signalling.

References

1. Ataxia telangiectasia: a review. Orphanet Journal of Rare Diseases (2016).
2. Genotype, extrapyramidal features, and severity of variant ataxia‐telangiectasia. Annals of Neurology (2019).
3. Clinical and genetic spectrum of Ataxia Telangiectasia Tunisian patients: Bioinformatic analysis unveil mechanisms of ATM variants pathogenicity. International Journal of Biological Macromolecules (2024).
4. The clinical spectrum of ataxia telangiectasia in a cohort in Sweden. Heliyon (2024).
5. ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects. Journal of Clinical Immunology (2025).