Phenotypic heterogeneity of Duplication Syndrome 22q11.2: relevance of genomic DNA analysis
Authors
DOI:
https://doi.org/10.37980/im.journal.ggcl.en.20252695Keywords:
22q11.2 duplication syndrome, chromosomal microarray, interstitial duplication, TOP3B geneAbstract
Background: 22q11.2 duplication syndrome (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, advances in chromosomal microarray analysis (CMA) offer a promising opportunity to improve detection, particularly in high-risk pregnancies. Case presentation: This report describes a female patient with dysmorphic features, neurodevelopmental delay, and behavioral alterations, with no related family history or consanguinity. Genetic findings: The patient was diagnosed with 22q11.2DupS through genomic DNA analysis using the Agilent® SurePrint G3 Human CGH+SNP array, which identified a heterozygous interstitial duplication at chromosomal coordinates 22q11.22 affecting the TOP3B gene, currently not associated with any known pathology but implicated in genomic stability and cellular aging. Discussion: 22q11.2DupS is a rare chromosomal disorder with a wide phenotypic spectrum, including intellectual disability, dysmorphic features, and congenital anomalies despite increasing recognition, comprehensive descriptions of its full clinical spectrum remain limited, and similar duplications have been classified with varying degrees of pathogenicity in public databases. Conclusion: 22q11.2DupS represents a complex clinical challenge due to its broad phenotypic spectrum, and early detection through advanced genetic testing such as CGH+SNP microarray analysis, along with genetic counseling and therapies including cognitive-behavioral and speech therapy, is essential for effective management as no specific therapies are available, treatment remains symptomatic.
References
[1] Barkit LE, et al. 22q11.2 duplications: Expanding the clinical presentation. Am J Med Genet A. 2022;188(3):779–87.
[2] Mary, L., et al. Prenatal phenotype of 22q11 micro-duplications: A systematic review and report on 12 new cases. Eur J Med Genet. 2022;65:104422.
[3] Schleifer CH. Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations. Neuropsychopharmacology. 2024;49(5):1024–32. doi:10.1038/s41386-023-01841-2.
[4] Balakrishnan RK, et al. A case of 22q11.2 microduplication syndrome with review of literature. Educ Adm Theory Pract. 2024;30(5):2256–2358.
[5] Mikulas C, et al. 22q11.2 duplication syndrome: A rare chromosomal disorder with variable phenotypical and clinical presentations. Scholar Pilot Valid Stud. 2023;4(1):14–7. doi:10.32778/SPVS.71366.2023.37.
[6] Verbesselt J, et al. Language profiles of school-aged children with 22q11.2 copy number variants. Genes. 2023;14(4):679.
[7] Jiang Y, et al. Prenatal diagnosis and genetic study of 22q11.2 microduplication in Chinese fetuses: A series of 31 cases and literature review. Mol Genet Genomic Med. 2024;12(1):e2498.
[8] Wang X, et al. Preliminary study of noninvasive prenatal screening for 22q11.2 deletion/duplication syndrome using multiplex dPCR assay. Orphanet J Rare Dis. 2023;18(1):278.
[9] Butensky A. Cardiac evaluation of patients with 22q11.2 duplication syndrome. Am J Med Genet A. 2021;185(3):753–8. doi:10.1002/ajmg.a.62011.
[10] Li H, Gong Y, Chen J, Xie L, Li B, Xiang Y, Xie M. Diagnosis of prenatal 22q11.2 duplication syndrome: a two-case study. J Genet. 2023;102(4).
[11] Jun KR. Deletion or Duplication Syndromes of Chromosome 22. J Interdiscip Genomics. 2024;6(1):1-5.
