Asymptomatic Bloom syndrome diagnosed by chance in a patient with breast cancer.

Bloom syndrome (BS) is a rare genetic disorder caused by biallelic inactivation of the BLM gene, which usually manifests in childhood by significant growth retardation, immune deficiency, characteristic skin lesions, cancer predisposition and other distinguishable disease features. To our knowledge, all prior instances of BS have been identified via intentional analysis of patients with clinical suspicion for this disease or DNA testing of members of affected pedigrees. We describe an incidental finding of BS, which occurred upon routine germline DNA analysis of consecutive breast cancer patients. The person with the biallelic pathogenic BLM c.1642C>T (p.Gln548Ter) variant remained clinically healthy for 38 years until she developed breast cancer. Detailed examination of this woman, which was carried out after the genetic diagnosis, revealed mild features of BS. A sister chromatid exchange (SCE) test confirmed the presence of this syndrome. The tumor exhibited triple-negative receptor status, a high proliferation rate, a low tumor mutation burden (TMB), and a moderate level of chromosomal instability (homologous recombination deficiency (HRD) score = 29). The patient showed normal tolerability to radiotherapy and several regimens of cytotoxic therapy. Thus, some BS patients may remain undiagnosed due to the mild phenotype of their disease. BLM should be incorporated in gene panels utilized for germline DNA testing of cancer patients.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)