Phenotypic heterogeneity of Duplication Syndrome 22q11.2: relevance of genomic DNA analysis

The 22q11.2DupS is a rare autosomal dominant disorder characterized by a broad spectrum of clinical manifestations, including intellectual disability, dysmorphic features, and congenital anomalies. The phenotypic heterogeneity of 22q11.2DupS complicates both clinical diagnosis and management. Traditional screening methods, such as fetal ultrasound, often fail to detect these abnormalities early, leading to delayed diagnoses. However, advancements in chromosomal microarray analysis (CMA) hold promise for improving detection, particularly in high-risk pregnancies.This report presents the case of a female patient with dysmorphias, neurodevelopmental delay and behavioral alterations without related family history or consanguinity. A diagnosed patient with 22q11.2DupS through genomic DNA analysis using the Agilent® SurePrint G3 Human CGH + SNP array. A heterozygous interstitial duplication was identified at chromosomal coordinates 22q11.22. This duplication affects the TOP3B gene, which is not currently associated with any known pathology but has been implicated in genomic stability and cellular aging. The 22q11.2DupS is a rare chromosomal disorder characterized by a broad spectrum of phenotypic manifestations, including intellectual disability, dysmorphic features, and congenital anomalies. Despite increasing recognition of this condition, comprehensive descriptions of its full clinical spectrum remain limited. Similar duplications have been classified with varying pathogenicity in public databases.In conclusion, 22q11.2DupS presents a complex clinical challenge due to its broad phenotypic spectrum. Early detection through advanced genetic testing, such as CGH + SNP array, genetic counseling, and therapies like cognitive-behavioral therapy and speech therapy, are essential for the effective management of the condition. As no specific therapies are available, treatment remains symptomatic.