Prenatal diagnosis, ultrasound characteristics and pregnancy outcomes of 16p11.2 deletion and duplication syndromes

Background Recurrent copy number variations (CNVs) in the 16p11.2 region are a prevalent cause of neurodevelopmental disorders. This study aims to investigate the prenatal phenotypic characteristics of 19 fetuses with 16p11.2 deletion/duplication syndromes and the results of single nucleotide polymorphism array (SNP-array) analysis. Methods We retrospectively analyzed 9671 pregnant women who underwent amniocentesis in Longgang Maternal and Child Health Hospital in Shenzhen from November 2018 to August 2025. SNP-array and G-banding karyotyping were performed on amniotic fluid samples from those pregnant women. The fetuses with 16p11.2 deletion/duplication detected by SNP-array were followed up. Results Out of the 9671 cases, 19 were diagnosed with 16p11.2 deletion/duplication, yielding a detection rate of 0.2%(19/9671). Among these cases, eleven fetuses exhibited a 16p11.2 deletion, while eight fetuses demonstrated a 16p11.2 duplication. Of these, eight deletions encompassed the proximal 16p11.2 region (BP4-BP5), while three deletions involved the distal 16p11.2 region (BP2-BP3). Among the eightidentified duplications, five encompassed the BP4-BP5 region, and two involved the BP2-BP3 region. Another case exhibited both proximal and distal duplications (BP2-BP5). Among the 19 cases diagnosed with 16p11.2 deletion or duplication, six cases exhibited structural abnormalities in different systems, includingtwo caseswith cardiovascular abnormalities, one case with cerebral abnormalities. Additionally, one fetus demonstrated pulmonary abnormalities, one presented clubfeet and another one presented with cleft lip and palate. Various ultrasound soft marker abnormalities were observed in five cases, including nuchal translucency thickening, lateral ventricular enlargement, single umbilical artery, and choroid plexus cyst. Eight cases showed no significant ultrasound abnormalities. Conclusions Fetuses possessing a 16p11.2 deletion or duplication demonstrate a broad spectrum of clinical features, characterized by incomplete penetrance and variable expressivity. In comparison to 16p11.2 duplication, individuals with a