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

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.

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.

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.

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.