Prenatal diagnosis of 1q21.1 microdeletions and microduplications: a retrospective case series

This study aimed to characterize the prenatal features, inheritance patterns, and outcomes of 1q21.1 copy number variations (CNVs) and refine prenatal counseling strategies.

We conducted a retrospective analysis of 20 consecutive prenatal cases diagnosed with 1q21.1 CNVs between 2017 and 2024. Genetic testing included karyotyping, chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq). Phenotypic data, inheritance patterns, and pregnancy outcomes were evaluated.

The cohort comprised 12 microdeletions (60%) and 8 microduplications (40%). Ultrasound anomalies were detected in 66.7% (8/12) of microdeletion cases (e.g., fetal growth restriction, cardiac defects) and 37.5% (3/8) of microduplication cases (e.g., nasal bone hypoplasia). No specific prenatal ultrasound markers pathognomonic for 1q21.1 CNVs were identified. Termination of pregnancy (TOP) was elected in 50% (10/20) of cases, predominantly for de novo CNVs (80% of TOP decisions). Among live-born infants (n = 9), no overt abnormalities were detected during postnatal follow-up (3 months to 5 years).

Prenatal 1q21.1 CNVs demonstrate incomplete penetrance and variable expressivity, without consistent association with specific prenatal ultrasound markers. The TOP rate for de novo CNVs reflects profound parental anxiety regarding neurodevelopmental outcomes. These findings underscore the critical need for comprehensive prenatal counseling that integrates genomic findings, phenotypic severity, and psychosocial support.