Pathophysiology
In healthy individuals, the human heart develops around the 20th day of gestation, when the outer endocardial tubes merge into a single cardiac tube. Thereafter, the cardiac tube begins to fold, developing into the atrium and ventricle. The right ventricle is dominant prior to birth, receiving 65% of the venous return to the heart, and is the main contributor of blood flow to the lower part of the body, the placenta, and the lungs. Though the exact cause of TOF is unknown, an association that has been observed is an anterior deviation of the infundibular septum that results in a misaligned VSD, with an overriding aorta causing a subsequent right ventricular obstruction.Different factors such as pulmonary stenosis can also contribute with the right ventricular outflow obstruction. During tet spells, a decrease in systemic vascular resistance or an increase in pulmonary resistance would be physiologically observed. The main anatomic defect in TOF is the anterior deviation of the pulmonary outflow septum. This defect results in narrowing of the right ventricular outflow tract (RVOT), override of the aorta, and a VSD. Four malformations
"Tetralogy" denotes four parts, here implying the syndromes four anatomic defects. This is not to be confused with the similarly named teratology, a field of medicine concerned with abnormal development and congenital malformations (including tetralogy of Fallot). Below are the four heart malformations that present together in tetralogy of Fallot:

There is anatomic variation between the hearts of individuals with tetralogy of Fallot.
In the famous Baltimore-Washington Study, it was reported that smoking more than one pack per day while pregnant was associated with two specific cardiac deflects, both part of TOF: pulmonary stenosis and transposition with VSD. Maternal diabetes: Maternal diabetes, diabetes Mellitus, and gestational diabetes are well-known risk factors of fetal CHD, including TOF. Maternal diabetes has been shown to increase the risk of cardiovascular deformations, namely the transposition of great arteries, one of the four deformations in TOF. Studies have also looked at whether diabetes increases the risk of malformation or poor sugar regulation and have found that sugar regulation does not significantly affect cardiac malformations. Retrospective studies have shown that diabetic mothers with good glucose control still retained the elevated CHD risk. Rubella: Rubella is characterized as mild, contagious viral disease with often unnoticed consequences. Infection with rubella during the first trimester has been seen to cause various fetal malformations, including TOF. Maternal Age: Older maternal age, especially after 35 can have various pregnancy risks due to existing co-morbidities such as hypertension, diabetes, hypothyroidism, and consanguinity. These risk factors can effect fetal development and lead to various fetal conditions such as CHD (including TOF), Down Syndrome and Autism.Embryology studies show that anterior malalignment of the aorticopulmonary septum results in the clinical combination of a ventricular septal defect (VSD), pulmonary stenosis, and an overriding aorta. : 200  Right ventricular hypertrophy develops progressively from resistance to blood flow through the right ventricular outflow tract.