A single misstep in cardiac development explains the co-occurrence of tetralogy of fallot and complete atrioventricular septal defect in Down syndrome.

Tetralogy of Fallot and a complete atrioventricular septal defect are thought to arise by distinct mechanisms, yet their co-occurrence is a recognized association. Analysis of the prevalence of co-occurrence in Down syndrome suggests a common developmental basis. Trisomy 21 may perturb cardiac progenitor cells before they enter the heart tube.