Chromosome 22q11.2 Microduplication Syndrome: A Review of the Literature and 12 New Cases

BACKGROUND/OBJECTIVES: 22q11.2 microduplication syndrome is a rare genetic disorder characterized by the presence of one or two additional copies of a segment within the 22q11.2 region of chromosome 22. While much of the literature has focused on the deletion variant leading to DiGeorge syndrome, the duplication counterpart has gained increasing attention due to its clinical variability and under-recognition. This review aims to deliver new possibilities to genetic counseling that can be provided in prenatal and postnatal cases as the phenotype of 22q11.2 microduplication carriers cannot be fully predicted. METHODS: In the present study, a total of 12 (5 prenatal and 7 postnatal) cases were diagnosed through array-CGH and combined with 679 (95 prenatal and 584 postnatal) cases reported in the literature. This review summarizes the published evidence available up to April 2025. Data on clinical presentations, genetic findings, diagnostic methodologies, and outcomes were extracted and analyzed. RESULTS: The combination of our cases and the reported cases with 22q11.2 microduplication syndrome revealed a broad phenotypic spectrum. Common clinical features include neurodevelopmental disorders, and cardiac anomalies. Importantly, the syndrome exhibits variable expressivity and reduced penetrance, with more than 70% of the findings to be inherited by one of the parents. CONCLUSIONS: 22q11.2 microduplication syndrome presents a heterogeneous clinical picture with variable expressivity and incomplete penetrance, posing challenges in diagnosis and genetic counseling, particularly when predicting prenatal outcomes. Awareness of its diverse manifestations is crucial for clinicians to consider this syndrome in the differential diagnosis and to provide informed counseling.