An insight into genetics of congenital heart defects associated with Down syndrome

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Agnish Ganguly Pinku Halder Upamanyu Pal Sujay Ghosh


Down syndrome is the most frequent live born human aneuploidy. Down syndrome is characterized by a set of phenotypically identified dysmorphism and various congenital malformations of which congenital heart defects is seen in about 50% of all cases. Atrio-ventricular Septal Defect is the most common form of congenital heart defect observed in Down syndrome. However, the exact molecular cause underlying the incidence of congenital heart defects and its differential phenotypic expression in DS are still not perfectly understood. In this review we have brought together findings from different studies and discussed multiple perspectives of the genetics of congenital cardiac defects in trisomy 21 background, viz., the contributions of triplicated dosage of chromosome 21 genes along with the effect of mutations in non- chromosome 21 disomic genes. Further, the roles of copy number variation and microRNAs have been discussed. We have also tried to shed light on the role of folate metabolism gene polymorphisms on congenital cardiac anomalies observed in Down syndrome. Lastly, we summarized the role of genes from different signaling pathways involved in cardiogenesis and also the recent developments in understanding of Down syndrome associated congenital heart defect from the studies on mice models. This review provides an overview regarding current state-of-art of knowledge related to Down syndrome associated congenital heart defects based on what have been discovered so far in this domain and hints at what prospect of research lies in this field in the future.

Keywords: Down syndrome, genetics of congenital heart defects, heart defects, genetics

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GANGULY, Agnish et al. An insight into genetics of congenital heart defects associated with Down syndrome. Medical Research Archives, [S.l.], v. 11, n. 4, apr. 2023. ISSN 2375-1924. Available at: <>. Date accessed: 29 may 2023. doi:
Review Articles


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