The cause(s) of most congenital heart diseases (CHDs) are unknown, although genetic studies suggest a

multifactorial etiology. A study from Portugal reported that methylene tetrahydrofolate reductase (MTHFR) gene
polymorphism can be considered a susceptibility gene for tetralogy of Fallot. [4, 5] A more recent study has
reported that VEGF genetic polymorphisms, -2578C>A and -634C>G, may be associated with an increased
risk for tetralogy of Fallot, whereas the risk is potentially reduced with 936C>T polymorphism. [6]
Prenatal factors associated with a higher incidence of tetralogy of Fallot (TOF) include maternal rubella (or
other viral illnesses) during pregnancy, poor prenatal nutrition, maternal alcohol use, maternal age older than
40 years, maternal phenylketonuria (PKU) birth defects, and diabetes. Children with Down syndrome also have
a higher incidence of tetralogy of Fallot, as do infants with fetal hydantoin syndrome or fetal carbamazepine
syndrome.
As one of the conotruncal malformations, tetralogy of Fallot can be associated with a spectrum of lesions
known as CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia).
Cytogenetic analysis may demonstrate deletions of a segment of chromosome band 22q11 (DiGeorge critical
region). Ablation of cells of the neural crest has been shown to reproduce conotruncal malformations.
These abnormalities are associated with the DiGeorge syndrome and branchial arch abnormalities.
The hemodynamics of tetralogy of Fallot depend on the degree of right ventricular (RV) outflow tract obstruction
(RVOTO). The ventricular septal defect (VSD) is usually nonrestrictive, and the RV and left ventricular (LV)
pressures are equalized. If the obstruction is severe, the intracardiac shunt is from right to left, and pulmonary
blood flow may be markedly diminished. In this instance, blood flow may depend on the patent ductus
arteriosus (PDA) or bronchial collaterals.

Diagnosis
Hemoglobin and hematocrit values are usually elevated in proportion to the degree of cyanosis. Patients with
significant cyanosis have the following, in association with a tendency to bleed:

Decreased clotting factors

Low platelet count
Diminished coagulation factors
Diminished total fibrinogen
Prolonged prothrombin and coagulation times
Arterial blood gas (ABG) results are as follows:

Oxygen saturation varies

pH and partial pressure of carbon dioxide (pCO2) are normal unless the patient is in extremis
Imaging studies include the following:

Echocardiography
Chest radiographs
Magnetic resonance imaging (MRI)
Echocardiography has the following attributes:

Color-flow Doppler echocardiography accurately diagnoses ductus arteriosus, muscular VSD, or atrial
septal defect

The coronary anatomy can be revealed with some degree of accuracy

Valvar alterations can be detected with ease

In many institutions, echocardiography is the only diagnostic study used before surgery
Chest radiographs have the following attributes:

Often normal initially

Diminished vascularity in the lungs and diminished prominence of the pulmonary arteries gradually
become apparent

The classic boot-shaped heart ( coeur en sabot) is the hallmark of the disorder
MRI has the following attributes:

Provides good delineation of the aorta, RVOT, VSDs, RV hypertrophy, and the pulmonary artery and
its branches [1]
Can also be used to measure intracardiac pressures, gradients, and blood flows