- The underlying developmental defect responsible for tetralogy of Fallot is the abnormal migration of neural crest cells.
- During normal cardiac development, neural crest cells play a crucial role in the formation and septation of the conotruncal region of the heart, which gives rise to the aorticopulmonary septum. This septum divides the outflow tract into the ascending aorta and pulmonary trunk.

- In tetralogy of Fallot, defective migration or improper development of these neural crest cells leads to anterior and cephalad deviation of the infundibular septum.
- This misalignment results in the characteristic features of tetralogy of Fallot, including:
1. Ventricular septal defect (VSD) - due to incomplete closure of the interventricular septum.

2. Pulmonary stenosis - caused by obstruction of the right ventricular outflow tract.

3. Overriding aorta - the aorta is displaced to lie directly over the VSD, receiving blood from both ventricles.

4. Right ventricular hypertrophy - due to increased workload from pulmonary stenosis.

The other options correlate with different congenital heart defects but are not responsible for tetralogy of Fallot.

- Failure of endocardial cushion fusion leads to atrioventricular septal defects.

- Defective septation of the primitive atrium causes atrial septal defects.

- Incomplete development of the sinus venosus is associated with sinus venosus atrial septal defects and abnormal venous connections.

Hence, knowing the role of neural crest cells in conotruncal septation is key to understanding the pathogenesis of tetralogy of Fallot.

Reference: Robbins Basic Pathology, 10th Edition, Chapter 10 – Cardiovascular Pathology, Page 385