Congenital heart defects among Down’s syndrome cases: an updated review from basic research to an emerging diagnostics technology and genetic counselling

Congenital heart defects (CHD) affect 50% of Down’s syndrome (DS) cases. This review focusses on the pathogenic molecular mechanism leading to the formation of DS-associated CHD along with the advancement of the emerging diagnostic techniques available for such patients in past few decades. We have shed light on the causative genes of DS-associated CHD that are located either on chromosome 21 or outside chromosome 21. Along with locus-specific mutation, numerous SNP and CNV, miRNA, use of maternal folic acid during pregnancy and signalling pathways are also reported to contribute to the formation of CHD in patients with DS. With the help of both these our understanding of pathogenic mechanism causing CHD in DS cases along with the availability of emerging technologies has facilitated a novel discovery that has ultimately provided a better treatment and management for such cases. Accurate diagnosis and treatment are now available with the introduction of CNV detection and NGS based approaches such as WES, WGS, target sequencing and sequencing of foetal cell-free DNA by the medical geneticist and cardiologist have now allowed further identification of familial recurrence risk and relatives who are at risk through genetic counselling, thereby providing reproductive options and improving proper care of DS-associated CHD. Further, gene-editing studies explore novel pathogenic mechanisms and signalling pathways in DS-associated CHD.