Prenatal Diagnosis of Sotos Syndrome: Integrating Chromosomal Microarray Analysis and Exome Sequencing

To present prenatal sonographic features, genomic results of chromosomal microarray analysis (CMA) and exome sequencing (ES), and pregnancy outcomes of fetuses with Sotos syndrome, and to provide genetic counseling for at-risk pregnancies.

This retrospective study analyzed 13 cases of prenatally diagnosed Sotos syndrome from January 2016 to March 2025. We collected and compared ultrasound findings, CMA and ES results, and pregnancy outcomes with the literature.

All 13 cases exhibited de novo abnormalities in the NSD1 gene, with nine deletions identified through CMA and four pathogenic/likely pathogenic variants detected via ES, two of which were novel. The observed phenotypes included increased nuchal translucency (NT) (5/13), central nervous system (CNS) anomalies (6/13), and growth abnormalities (2/13). Additionally, polyhydramnios, cardiac anomalies, and renal anomalies were also noted. All pregnancies resulted in termination.

Sotos syndrome presents with nonspecific symptoms during the early stages of gestation, except for increased NT. However, CNS anomalies begin to appear during the second and third trimesters. Furthermore, polyhydramnios should be noted. A comprehensive prenatal diagnosis of Sotos syndrome can be made through ultrasound and genetic testing.