Near-Comparable Frequency of rob(21;21) and rob(14;21) Translocations in Trisomy 21: A Retrospective Cytogenetic Analysis of 9,313 Cases From an Indian Referral Cohort

Background Chromosomal abnormalities are one of the leading causes of developmental delay, congenital anomalies, and reproductive failure. Cytogenetic evaluation aids diagnosis, genetic counselling, and prevention. This study evaluated the cytogenetic and demographic profile of chromosomal abnormalities, with a focus on Down syndrome (DS, trisomy 21), in a large referral cohort. Methodology A retrospective analysis of 9,313 blood samples was performed using GTG-banding karyotyping. Clinical indications, age, sex, and diagnostic yield were evaluated to identify frequency patterns and etiological trends. Results Among 9,313 samples analyzed, 1,597 (17.1%) were diagnosed with DS. A male predominance was observed, with 968 (60.6%) males and 629 (39.4%) females. Classical free trisomy 21 (47,XX,+21/47,XY,+21) comprised 1,465 (91.7%) cases, while Robertsonian translocations accounted for 90 (5.6%). Other forms, including mosaicism and double aneuploidy, constituted 42 (2.6%). Among Robertsonian cases, rob(14;21) and rob(21;21) were the most frequent subtypes. In most cases, 933 (58%) were diagnosed within the first six months of life. Referral indications included clinical suspicion of trisomy 21 in 605 (38%) cases, unassigned clinical history in 460 (29%) cases, prenatal screening in 220 (14%) cases, anatomical anomalies in 75 (5%) cases, abnormal antenatal ultrasound findings in 86 (5%) cases, disorders of sex development in 16 (1%) cases, and other indications in 135 (8%) cases. Conclusions DS remains the most common autosomal aneuploidy, primarily resulting from meiotic nondisjunction. The observed male predominance and increasing referrals based on prenatal screening highlight the continued importance of cytogenetic evaluation in clinical practice. Integration of cytogenetic findings with clinical assessment is essential for accurate diagnosis, genetic counselling, and informed reproductive decision-making. The identification of Robertsonian translocations in this cohort reinforces the need for parental karyotyping to determine whether the rearrangement is inherited or de novo. In our practice, parental karyotyping is recommended in all cases of trisomy 21 to distinguish classical (free) trisomy from translocation-associated trisomy 21, thereby enabling accurate recurrence risk assessment in future pregnancies.