Our work demonstrates that CS-associated variants in both kcnj8 and abcc9 lead to a remarkable combination of cardiovascular anomalies in zebrafish, such as enlarged, hypercontractile ventricles with increased cardiac output, elevated occurrence of pericardial edema, reduced blood vein flow velocity, and cerebral vasodilation and tortuosity. This evidence concerns the gene KCNJ8 and Cowden syndrome 1.