MAPK8 and congenital heart disease: Although most of the data point towards a hemodynamic overload of the DS hearts with septal defects as the cause of these changes, recent research has identified two major signaling hubs, JNK and NF-kB able to transduce cytokine signaling in the vertebrate myocardium and having a significant ethiopathogenic potential in children with congenital heart defects [64].