Incidental Constitutional Chromosomal Abnormalities Identified in Bone Marrow Chromosome Analysis: A Large-Scale...

Constitutional chromosomal abnormalities detected during bone marrow (BM) chromosome analysis may be misclassified as acquired abnormalities. Although incidental findings identified through somatic tissue testing are increasingly recognized, data on incidental constitutional chromosomal abnormalities remain limited.

We retrospectively reviewed BM chromosome studies performed during 1999-2025 at Asan Medical Center, encompassing 29,733 individuals. Chromosomal abnormalities reported as constitutional, based on germline confirmation or BM cytogenetic findings strongly suggesting a constitutional origin, were included. Cases without clinical recognition were classified as incidental. The cytogenetic spectrum, age at detection, prognostic impact, and follow-up testing were analyzed.

Constitutional chromosomal abnormalities were identified in 83 individuals (0.28%). Trisomy 21 was the most frequent abnormality (N=32), followed by sex chromosome abnormalities (N=16), reciprocal translocations (N=15), Robertsonian translocations (N=7), unbalanced structural abnormalities (N=7), and others (N=6). Among constitutional cases, 47 were identified as incidental (0.16% of total cohort). Only 16% of constitutional trisomy 21 cases were incidental. Individuals with incidental abnormalities were older than those with known constitutional abnormalities (median age, 24 vs. 2 yrs; P <0.001). Family testing was infrequently performed, occurring in five of 15 germline-confirmed cases (33.3%), all of whom were pediatric patients. In hematologic malignancies, inclusion of incidental constitutional abnormalities altered cytogenetic risk classification in five cases.

Although incidental constitutional chromosomal abnormalities are rare, these abnormalities can influence prognostic assessment and downstream clinical management. Therefore, accurate recognition and appropriate confirmation are essential for optimal interpretation.