Tetralogy of Fallot, the most common type of cyanotic (causing bluish discoloration of the skin) congenital (present at birth) heart condition, occurs when structural abnormalities within the heart cause blue (deoxygenated) blood to mix with red (oxygenated) blood in the body.

A patient with tetralogy of Fallot has four specific structural heart issues, all related to one underlying embryonic change, that prevent blood from flowing through the heart in its normal way (more on that below).

Tetralogy of Fallot is named after French doctor Etienne-Louis Arthur Fallot, who described the condition’s four heart abnormalities in great detail at the end of the 19^th century. The prefix “tetra” means “four” in Greek.

In the United States, about 1,600 babies are born with tetralogy of Fallot each year. The condition, which is typically diagnosed within the first year of life, affects males and females equally.

Surgical treatments can correct the heart defects associated with the condition. Most patients who are treated in infancy or early childhood live well into their adult years. For example, a study of patients with tetralogy of Fallot who underwent surgical repair in early childhood between 1986 and 2007 had a survival rate of approximately 95% at 10 years and 93% at 25 years.

“Our center at Yale New Haven Hospital cares for adults living with tetralogy of Fallot well into their 70s,” says Robert Elder, MD, a Yale Medicine specialist in congenital heart disease.

Tetralogy of Fallot is a birth defect affecting the structure of the heart. Four different abnormalities are present in a patient’s heart, which changes how blood travels through it, preventing the proper amount of oxygen-rich blood from circulating through the body.

Below are the four structural abnormalities associated with tetralogy of Fallot:

• Ventricular septal defect (VSD), a large hole in the wall that separates the ventricles (the lower chambers of the heart). A VSD prevents the heart from separating oxygen-rich from oxygen-poor blood.
• Pulmonary stenosis, a narrowing or obstruction of the pulmonary valve, which connects the right ventricle and the pulmonary artery (the main artery that blood travels through to the lungs to pick up oxygen). In some cases, the pulmonary valve does not form during development, which completely obstructs blood flow.
• Overriding aorta, in which the aorta (the large artery that brings oxygen-rich blood from the heart to the body) is moved more anteriorly than it should be. Normally, blood that exits the left side of the heart through the aortic valve enters the aorta. In a patient with tetralogy of Fallot, the aorta is positioned straddling the VSD, allowing oxygen-rich and oxygen-poor blood to mix as it is pumped to the body.
• Right ventricular hypertrophy, a thickening of the muscle wall of the right ventricle, as a result of the muscle working harder to pump blood.

In combination, these structural abnormalities lead to cyanosis, or blue discoloration of the systemic blood.

In a person with a normal heart, oxygen-poor (low in oxygen) blood that travels to the heart enters the heart’s right atrium (upper right chamber) and then travels to the right ventricle (lower-right chamber). Blood then goes through the pulmonary valve to the main pulmonary artery, where it picks up oxygen in the lungs. Next, the oxygenated blood passes into the heart’s left atrium (upper left chamber) on its way to the left ventricle (lower left chamber). Finally, it passes through the aortic valve to the aorta, where the oxygen-rich blood is sent throughout the body.

In a person with tetralogy of Fallot, the four structural abnormalities mentioned above make it difficult for enough blood to become oxygenated. This limits the heart’s ability to send oxygenated blood to the rest of the body, where cells and organs need oxygen to function. The skin appears blue because a limited amount of oxygen-rich blood flows through the body.

Babies with tetralogy of Fallot may experience “tet spells,” which are sudden, potentially life-threatening instances when the skin becomes even more bluish, coupled with difficulty breathing; it occurs when babies cry, eat, or have bowel movements. In these moments, more blood than usual may travel through the VSD, resulting in even less oxygen-rich blood traveling throughout the body. Tet spells may cause fainting.

About two-thirds of babies who don’t receive surgical intervention for tetralogy of Fallot die from complications relating to lack of oxygen during tet spells.

Tetralogy of Fallot is often caused by genetic or chromosomal abnormalities, but the reasons why they occur are still poorly understood. Around 15% of tetralogy of Fallot cases occur in people with the following syndromes:

• Down syndrome (caused by an extra partial or full copy of chromosome 21)
• Alagille syndrome (caused by a mutation of the JAG1 gene or, less commonly, the NOTCH2 gene)
• 22q11.2 deletion syndrome also called DiGeroge syndrome and velocardiofacial syndrome, among several other names (caused by the deletion of a small piece of chromosome 22 at a location of the chromosome labeled q11.2)

Tetralogy of Fallot is also associated with mutations in certain other genes that are not associated with a syndrome.

Patients with tetralogy of Fallot experience symptoms including:

• Bluish skin
• Difficulty breathing while eating
• Poor growth
• Shortness of breath
• A heart murmur
• Tet spells
• Clubbed fingers or toes (when the fingertips or tips of the toes bulge and the nail beds become rounded) if the condition goes untreated for 2 to 3 years after birth

Most cases are easily diagnosed at birth due to symptoms, cyanosis, or newborn screening for critical congenital heart disease.

Certain chromosomal or genetic conditions may increase the risk of tetralogy of Fallot, including:

• Down syndrome (trisomy 21)
• DiGeorge syndrome (22q11.2 microdeletion syndrome)
• Trisomy 13
• Trisomy 18
• Alagille syndrome
• CHARGE syndrome
• VACTERL association
• Holt-Oram syndrome
• NK2 homeobox 5 gene mutation
• GATA4 gene mutation
• GATA6 gene mutation
• Forkhead box transcription factor 1
• Teratocarcinomaderived growth factor 1
• Growth differentiation factor 1.125
• Copy-number variants to chromosomes 22q11.2, 3p25.1, 1q21.1, and 7p21.3
• Copy-number variants to the plexin A2 gene
• A family history of tetralogy of Fallot or congenital heart disease

The risk of tetralogy of Fallot may increase if certain conditions occur during pregnancy, including:

• Uncontrolled diabetes in the mother
• Untreated phenylketonuria in the mother

About 60% of the time, tetralogy of Fallot is diagnosed before birth. During a routine ultrasound halfway through pregnancy, doctors may notice structural abnormalities in the fetus’s heart that make them take a closer look. Doctors can order a fetal echocardiogram, an ultrasound exam that focuses on the fetus’s heart. (Both ultrasound exams use sound waves to create images of a fetus’s organs by placing a transducer, or wand, on the pregnant mother’s belly.) A fetal echocardiogram can show that specific structural abnormalities are present in the heart and that blood is not traveling through the heart on the expected path.

In other instances, tetralogy of Fallot is diagnosed after birth. Doctors can diagnose the condition by learning about a patient’s medical history, performing a physical examination, and conducting diagnostic tests.

While learning about a patient’s medical history, doctors will ask about the baby’s symptoms, including when their skin has appeared blue and if there have been any tet spells with more significant blueness, along with difficulty breathing. Doctors should also ask if there is a family history of tetralogy of Fallot, other congenital heart disorders, or other genetic or chromosomal abnormalities.

During a physical exam, doctors listen for a heart murmur via a stethoscope. (A murmur may not be present in newborns.) Doctors look for symptoms of the condition, including bluish skin, breathing difficulties, and poor growth.

These diagnostic tests can be used to confirm that a patient has tetralogy of Fallot:

• Pulse oximetry. Patients with tetralogy of Fallot have lower-than-normal blood-oxygen levels. A pulse oximeter, which is attached briefly to an infant’s hand or foot, can measure oxygen levels in the blood.
• Electrocardiogram (ECG or EKG). Doctors use this test to record the heart’s electrical activity. It can show whether the heart is functioning properly or abnormally. Doctors attach sticky sensors to the patient’s chest and torso to get readings from the heart. If a patient has tetralogy of Fallot, the electrocardiogram may be abnormal.
• Chest X-ray. If a patient has tetralogy of Fallot, X-ray images will show that the heart is shaped abnormally, like a boot.
• Echocardiogram (sometimes known as an “echo”). During this test, which is an ultrasound study of the heart, a sonographer (a medical professional who administers ultrasounds) moves a transducer over the patient’s chest and torso to create images of the heart on a screen. The images can diagnose tetralogy of Fallot.

Surgical intervention is used to correct tetralogy of Fallot, but it is usually performed between 2 and 6 months of life. Younger infants may need medication to manage their symptoms until they are old enough for surgery.

Doctors may prescribe prostaglandins in certain newborns with symptoms of tetralogy of Fallot and severe cyanosis. This medication prevents the ductus arteriosus—a special blood vessel that connects the pulmonary artery to the aorta in a fetus—from closing during the first week of life. Keeping this blood vessel open can allow more oxygen-rich blood to circulate through the body until the condition can be surgically addressed. This can be extremely important if the pulmonary valve is completely blocked or absent. After the ductus arteriosus has closed, doctors may place a shunt or a stent within the heart to temporarily connect the pulmonary artery and aorta. This may be done with minimally invasive catheterization—inserting thin tubes with a camera and necessary equipment into a blood vessel in the groin, then threading them through blood vessels until they reach the heart, where the shunt or stent can be placed.

Patients who experience tet spells need to be treated quickly. Doctors position the patient’s knees to their chest, which helps change the blood flow through the heart, enabling more oxygen to circulate through the body. Some patients may need intravenous phenylephrine, supplemental oxygen, or intravenous hydration to improve tet spell symptoms. Beta-blockers may be prescribed to reduce future instances of tet spells.

When a patient is old enough for surgical repair, doctors perform open-heart surgery. They close the ventricular septal defect, along with the ductus arteriosus (if it was kept open with medication). They also relieve obstruction across the pulmonary valve, enabling increased blood flow to the pulmonary artery so blood can become oxygenated. Doctors may also enlarge or widen the pulmonary artery. Eventually, the right ventricle returns to its normal size because these fixes eliminate the need for it to work harder than normal.

Well over 90% of patients who have surgical intervention to correct the condition live into adulthood as healthy, active people. If the condition isn’t treated, however, people with tetralogy of Fallot often die by age 20.

Patients with tetralogy of Fallot need to see a cardiologist regularly throughout their lives, even if the condition was surgically corrected.

Some adults who previously had surgery to repair tetralogy of Fallot may develop a leak in their pulmonary valve, so they may need additional surgery to repair or replace the valve.

Some patients who have their tetralogy of Fallot surgically treated develop heart-rhythm problems (arrhythmias). Medications, devices, or procedures may help manage arrhythmias.

Patients with tetralogy of Fallot are at increased risk of endocarditis, an inflammation of the heart lining.

“Yale has a long history of treating tetralogy of Fallot, dating back to the early surgical era in the 1940s,” says Dr. Elder. “In the modern era, we offer all the latest surgical and transcatheter advances to care for individuals with tetralogy. Our team routinely performs surgery and interventions on the entire spectrum of tetralogy of Fallot patients, from neonates less than 1 month of age to adults living into their 7^th decade and beyond.”