Prenatal genetic analysis of fetal aberrant right subclavian artery with or without additional ultrasound anomalies in a third level referral center

To evaluate the correlation between chromosomal abnormalities and fetal aberrant right subclavian artery (ARSA) with or without additional ultrasound anomalies (UAs). A total of 340 fetuses diagnosed with ARSA by ultrasound between December, 2015, and July, 2021, were included. All cases were subdivided into three groups: (A) 121 (35.6%) cases with isolated ARSA, (B) 91 (26.8%) cases with soft markers, and (C) 128 (37.6%) cases complicated with other UAs. Invasive testing was performed via amniotic fluid or cord blood karyotyping and chromosomal microarray analysis (CMA) in parallel, and pregnancy outcomes were followed. Karyotype abnormalities were identified in 18/340 (5.3%) patients. Karyotype abnormalities in Groups A, B, and C were 0/121 (0.0%), 7/91 (7.7%), and 11/128 (8.6%), respectively. CMA abnormalities with clinically significant variants were detected in 37/340 (10.9%) cases, of which 22q11.2 deletion syndrome and trisomy 21 accounted for 48.6% (18/37). The overall abnormal CMA with clinically significant variant detection rates in Groups A, B, and C were 3/121(2.5%), 13/91 (14.3%), and 21/128 (16.4%), respectively. There were significant difference in clinically significant CMA anomalies detection rate between Groups A and C (p < 0.05), as well as Groups A and B (p < 0.05). Comparing CMA to karyotyping showed a clinically significant incremental yield in Group C (7.8%, 10/128) compared to Groups A (2.5%, 3/121) and B (6.6%, 6/91) (p > 0.05). Fetal ARSA with additional UAs, concurred with cardiac and extra-cardiac anomalies, constitutes a high-risk factor for chromosomal aberrations, especially for pathogenic or likely pathogenic copy number variants.