Prenatal Findings in 22q11.2 Duplication Syndrome: a retrospective analysis of eight fetuses and review of the literature

Abstract

Objective: To characterize prenatal findings in fetuses with 22q11.2 duplication syndrome and explore their outcomes. Methods: We evaluated fetuses with 22q11.2 duplication identified through prenatal genetic testing (2020-2023). Prenatal ultrasound results, autopsy findings, inheritance of the duplications, and outcome were examined and compared with existing literature. Results: We report eight cases of 22q11.2 duplication identified by prenatal aCGH test, with increased nuchal translucency as the primary indication (n=4). Other relevant findings were microcephaly and intra-uterine growth restriction (n=1), and bilateral ventriculomegaly (n=1). Inheritance patterns included maternal or paternal transmission (n=6), de novo occurrence (n=1), and unknown origin (n=1). Termination of pregnancy was performed in three cases with musculoskeletal and craniofacial anomalies in autopsy. Postnatal follow-up (n=5) revealed diverse phenotypes ranging from healthy children with adequate growth pattern and minor phenotypic alterations (n=3), poor growth, dolichocephaly and hip dysplasia (n=1), and psychomotor delay (n=1). Two cases had history of low schooling and learning difficulties in the relatives who carried the duplication. Conclusions: Our research contributes for a better characterization of 22q11.2 duplication syndrome. The study emphasizes the importance of considering the variable expressivity and incomplete penetrance associated with this duplication, highlighting the need for comprehensive prenatal genetic counselling.