Further, the low level of CITED2 protein may weaken the combination of CITED2 and ISL1 leading to VSD leading to VSD,26, 28, 29 and may overexpress TFAP2 family,12, 26 causing low expression of Pitx2 that hinders the formation of a normal heart and increases the risk of VSD.12, 26. Here, ISL1 is linked to ventricular septal defect.