Classic Ataxia-Telangiectasia associated with a homozygous missense ATM variant: A case report

Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risk Reporting the phenotypic spectrum of ATM variants is essential to refine genotype-phenotype correlations. We report a 6-year-old boy presenting with progressive gait ataxia, recurrent respiratory infections, chronic otorrhea, and conjunctival telangiectasias. Laboratory studies revealed immunodeficiency with reduced IgG and IgA, and elevated IgM. Brain MRI showed mild cerebellar atrophy, while chest X-ray revealed bilateral interstitial infiltrates. Whole-exome sequencing identified a homozygous missense variant in ATM (c.4940 T > G; p.Leu1647Arg), currently classified as a variant of uncertain significance (VUS); this represents only the second reported family with this variant.The patient improved with intravenous antibiotics and IVIG. Family genetic testing was recommended given parental consanguinity and an affected sibling. This case illustrates the classical phenotype of A-T with immunodeficiency and neurological dysfunction. Such cases reinforce genotype-phenotype correlations and may guide diagnosis and counseling. Although the variant's pathogenicity remains to be functionally validated, its clinical correlation supports disease relevance. Careful clinical and familial correlation of ATM variants is crucial for advancing diagnostic precision, genetic counseling, and future therapeutic strategies in A-T.