[Prenatal ultrasound and genetic characteristics of 60 fetuses with 16p11.2 microdeletion]

The postnatal phenotypes of fetuses with 16p11.2 microdeletion mainly include autism spectrum disorder, schizophrenia, and intellectual disability, often accompanied by obesity and congenital malformations. However, studies on the prenatal phenotypes of fetuses with 16p11.2 microdeletion remain limited. This study aims to investigate the correlation between prenatal ultrasound findings and genetic characteristics of fetuses with 16p11.2 microdeletion, thereby providing evidence for clinical genetic counseling.

Clinical data of 60 fetuses prenatally diagnosed with 16p11.2 microdeletion at multiple centers between October 2016 and December 2024 were collected. Data included maternal age, indications for amniocentesis and gestational age at testing, fetal ultrasound findings, and copy number variation sequencing (CNV-seq) results. CNV-seq was also performed in both parents to determine the origin of the variants. Pregnancy outcomes were followed up for all cases. Based on prenatal ultrasound findings, genetic test results, and pregnancy outcomes, the prenatal phenotypes and genomic characteristics of fetuses with 16p11.2 microdeletion were systematically analyzed.

Among 43 721 fetuses who underwent CNV-seq testing, 60 cases of 16p11.2 microdeletion were identified (60/43721, 0.14%). Of these, 49 cases had proximal deletions (BP4-BP5), 9 had distal deletions (BP2-BP3), and 2 had large deletions (BP2-BP5). Among the 49 fetuses with proximal 16p11.2 deletions (BP4-BP5), 18 had structural abnormalities, including 6 cases of hemivertebra with scoliosis, 4 cases of renal developmental abnormalities, 2 cases of coarctation of the aorta, and 6 cases of other abnormalities. Twenty-six fetuses presented with ultrasound soft markers, including 11 cases of increased nuchal translucency (NT) thickness (1 accompanied by a single umbilical artery), 6 cases of mild ventriculomegaly (1 accompanied by polyhydramnios), and 9 cases of other soft markers. Five fetuses showed no ultrasound abnormalities. Among the 9 fetuses with distal 16p11.2 deletions (BP2-BP3), 2 had intrauterine growth restriction, 4 presented with ultrasound soft markers (2 with absent nasal bone, 1 with a single umbilical artery, and 1 with increased NT thickness), and 3 had no ultrasound abnormalities. Among the 2 fetuses with large 16p11.2 deletions (BP2-BP5), 1 presented with congenital diaphragmatic hernia and the other with increased NT thickness. Of the 50 cases, 72% (36/50) were de novo variants and 28% (14/50) were inherited from a parent. Regarding pregnancy outcomes, 67% (35/52) of pregnancies were terminated.

Prenatal ultrasound phenotypes of fetuses with 16p11.2 microdeletion are highly heterogeneous. Proximal 16p11.2 deletions (BP4-BP5) are primarily associated with hemivertebra accompanied by scoliosis, renal developmental abnormalities, and increased NT thickness. In contrast, distal 16p11.2 deletions (BP2-BP3) may be associated with intrauterine growth restriction and ultrasound soft markers.