Prenatal Genetic and Sonographic Features of KBG Syndrome: A Cohort Study of 19 Fetal Cases

Abstract

ABSTRACT Objective To characterize prenatal sonographic features, genomic findings from chromosomal microarray analysis (CMA) and whole‐exome sequencing (WES), pregnancy outcomes, and postnatal manifestations in KBG syndrome and to provide evidence for prenatal diagnosis and genetic counseling in at‐risk pregnancies. Methods A retrospective analysis was performed on the clinical data of 19 fetuses with KBG syndrome. Sonographic findings, CMA/WES results, and pregnancy outcomes were collected, summarized, and compared with published literature. Results CMA identified 7 fetuses with 16q24.3 microdeletions, including 5 affecting non‐coding exons 1–2. WES detected 12 ANKRD11 variants, including 11 loss‐of‐function and 5 novel variants. The main sonographic features included fetal growth restriction (FGR, 36.8%) and increased nuchal translucency (NT, 26.3%). Ventricular septal defects, pericardial effusion, central nervous system (CNS), and renal malformations were each observed in 15.8% of fetuses, whereas skeletal abnormalities were identified in 10.5%. Multiple sonographic anomalies were observed in some individuals. Of 19 affected pregnancies, 15 were electively terminated, and 4 resulted in live births. Conclusion KBG syndrome shows heterogeneous prenatal manifestations, with FGR and increased NT being the most prevalent. 16q24.3 microdeletions and ANKRD11 loss‐of‐function variants are major genetic causes. Deletions involving non‐coding exons 1–2 likely result in ANKRD11 gene haploinsufficiency. A combined approach of prenatal sonography, CMA, and WES is essential for accurate diagnosis, informed counseling, and management.