Contrasting outcomes of 16p11.2 microdeletion and microduplication in prenatal diagnosis: phenotypic variability and genetic counseling strategies

Background Copy number variations (CNVs) in the 16p11.2 region are associated with neurodevelopmental disorders, but they exhibit incomplete penetrance and variable expressivity. Prenatal diagnosis of these CNVs presents significant challenges because of the unpredictable phenotypic outcomes. Materials and methods We retrospectively analyzed two fetal cases diagnosed prenatally via amniocentesis with CNV sequencing (CNV-seq) as having 16p11.2 CNVs, and discussed them in the context of current literature. In this research, GTG-banding karyotype analysis, CNV-seq, and whole-exome sequencing were performed. Results Case 1 had a de novo 16p11.2 microdeletion [del(16)(p11.2)] accompanied by an ultrasound soft marker (absent nasal bone); the pregnancy was terminated after genetic counseling. Case 2 carried a de novo 16p11.2 microduplication [dup(16)(p11.2)] and was born with a normal phenotype to date. Conclusion 16p11.2 microdeletion and microduplication syndromes exhibit significant phenotypic heterogeneity and incomplete penetrance. When such CNVs are identified prenatally, integrated management – including parental testing, detailed fetal imaging, and comprehensive, nondirective genetic counseling – is essential to provide families with individualized risk assessment and support informed decision-making.