Embryological Mechanisms of Teratology of Fallot
Tetralogy of Fallot
Tetralogy of Fallot is a congenital heart lesion characterized by a constellation of four morphologic abnormalities present in the newborn heart. These features include a ventricular septal defect, overriding aorta, pulmonary stenosis, and right ventricular hypertrophy. Together, these defects result in decreased pulmonary blood flow, leading to cyanosis in the newborn.
Improper Cardiac Septation Events
Subsequent to the lateral folding and looping events that give rise to the primitive heart tube are a series of complex septation processes that will ultimately complete morphogenesis of the four chambered heart. Thus, the goals of cardiac septation are two-fold:
- To create four distinct cardiac chambers
- To correctly position the great vessels relative to these chambers
Improper execution of these septation events can give rise to many congenital heart defects, such as Tetralogy of Fallot.
Morphologic Basis for Teratology of Fallot
The morphologic basis for Tetralogy of Fallot is the result of improper positioning of the outlet septum. In the normal heart, the outlet septum is an indistinguishable component of the crista supraventricularis that communicates with the septomarginal trabeculae to divide the right and left ventricular cavities. In Tetralogy of Fallot, proper ventricular septation is perturbed by anterocephalad displacement of the outlet septum relative to the septomarginal trabecula. The direct consequence of this malalignment is an overriding aortic orifice and a ventricular septal defect, resulting in an intracardiac right to left shunt of blood. In addition, anterocephalad displacement of the outlet septum indirectly predisposes the pulmonary trunk to stenosis in the setting of septoparietal trabecular hypertrophy. Together, the displacement of the outlet septum coupled with the hypertrophic arrangement of the septoparietal trabeculae account for the three anatomical cardinal defects in Tetralogy of Fallot - aortic dextroposition, interventricular communication (VSD), and pulmonary stenosis. The fourth defect - right ventricular hypertrophy - is a hemodynamic consequence of these three morphologic changes, as the right ventricle physiologically adapts to the increased resistance of a stenotic pulmonary trunk.