August 18, 2016
Years published: 1986, 1994, 1995, 1996, 2003, 2016
NORD gratefully acknowledges Mary C. Mancini, MD, PhD, Department of Surgery, Louisiana State University Health Sciences Center, for assistance in the preparation of this report.
Tetralogy of Fallot is the most common form of cyanotic congenital heart disease. Cyanosis is the abnormal bluish discoloration of the skin that occurs because of low levels of circulating oxygen in the blood. Tetralogy of Fallot consists of the combination of four different heart defects: a ventricular septal defect (VSD); obstructed outflow of blood from the right ventricle to the lungs (pulmonary stenosis); a displaced aorta, which causes blood to flow into the aorta from both the right and left ventricles (dextroposition or overriding aorta); and abnormal enlargement of the right ventricle (right ventricular hypertrophy). The severity of the symptoms is related to the degree of blood flow obstruction from the right ventricle.
The normal heart has four chambers. The two upper chambers known as atria are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The valves allow for blood to be pumped through the chambers. Blood travels from the right ventricle through the pulmonary artery to the lungs where it receives oxygen. The blood returns to the heart through pulmonary veins and enters the left ventricle. The left ventricle sends the now oxygen-filled blood into the main artery of the body (aorta). The aorta sends the blood throughout the body.
Ventricular Septal Defect
The heart has an inner wall that separates the two chambers, called a septum. The septum stops mixing of the blood between the two sides. A ventricular septal defect is a hole in the septum that causes oxygen-rich blood (left ventricle) and the oxygen-poor blood (right ventricle) to mix.
This defect is the narrowing of the pulmonary valve, which flows oxygen poor blood into the pulmonary artery and from there the blood travels to the lungs to pick up oxygen. Pulmonary stenosis is when the pulmonary valve cannot open fully, making the heart work harder and results in a lack of blood reaching the lung.
Right Ventricular Hypertrophy
The muscle of the right ventricle is thicker due to the right side of the heart receiving excessive blood flow from the left side of the heart through the ventricular septal defect and working harder.
In a normal heart, the aorta is attached to the left ventricle and allows oxygen-rich blood to flow throughout the body. In a tetralogy of Fallot heart, the aorta is located between both the left and the right ventricle. This causes oxygen-poor blood from the right ventricle to flow into the aorta instead of the pulmonary artery. If infants with tetralogy of Fallot are not treated, the symptoms usually become progressively more severe. Blood flow to the lungs may be further decreased and severe cyanosis may cause life-threatening complications. The exact cause of tetralogy of Fallot is not known.
The symptoms of tetralogy of Fallot vary widely from person to person. The severity of the symptoms, which may range from mild to severe, is related to the degree of blood flow obstruction from the right ventricle.
Tetralogy of Fallot may be present at birth or emerge within the first year of life. The most common symptom of this disorder is abnormal bluish discoloration of the skin (cyanosis). This may occur while the child is at rest or crying. The mucous membranes of the lips and mouth, fingertips, and toenails may be particularly blue due to the lack of oxygen. Affected infants may have difficulty breathing (dyspnea); as a result, they tend to play for short periods and then rest. Other symptoms may include a heart murmur, easy fatigability, poor appetite, slow weight gain, heart murmurs, an abnormal increase in the numbers of red blood cells (polycythemia), fingers and toes with wide, enlarged tips and overhanging nails (clubbing), and/or delayed physical growth.
Some infants with tetralogy of Fallot may experience episodes of severe cyanosis and breathing difficulty (paroxysmal hypercyanotic attack or “blue” or “tet” spells). During these episodes, the infant may become restless, extremely cyanotic while gasping for air and nonresponsive to parent’s voices. In extreme situations, infants may pass out. A characteristic squatting position may be assumed to help assist breathing. Severe attacks may lead to the loss consciousness, and occasionally to convulsions or temporary paralysis on one side of the body (hemiparesis). These spells may last for a few minutes to a few hours and may be followed by periods of muscle weakness and a prolonged period of sleep.
A variety of other complications may occur in association with tetralogy of Fallot. These may include mild anemia in infants, abnormal increase in the number of red blood cells (polycythemia) in older children, and blood clotting (coagulation) defects. These blood abnormalities may lead to the formation of blood clots that can travel through the blood stream (embolisms). These blood clots may cause the blood supply to the brain (cerebral infarctions) to be interrupted temporarily.
Additional complications may include infectious inflammation of the sinuses (sinusitis) and brain abscesses. In some cases, the connection between the aorta and the pulmonary artery, which normally closes before birth, may remain open (patent ductus arteriosus). The symptoms associated with this condition vary depending upon the size of the opening and may include rapid breathing, frequent respiratory infections, and easy fatigability. Congestive heart failure is rare, except in association with bacterial infection of the heart (endocarditis) or abnormal heart rhythms (arrhythmias). However, a common sign is a heart murmur, or an extra sound heard while listening to the heartbeat.
The most severe form of tetralogy of Fallot is known as pseudotruncus arteriosus. Infants with this form of the disorder experience severe symptoms that relate to the profound obstruction of the right ventricular blood flow and severe underdevelopment of associated blood vessels and valves related to the lungs (pulmonary atresia). Ventricular septal defects are usually severe in this form of the disorder. Severe cyanosis, alarmingly low levels of circulating oxygen, and excessive circulating red blood cells (polycythemia) are the major features of pseudotruncus arteriosus. (For more information, see “Ventricular Septal Defect” in the Related Disorders section of this report.)
The exact cause of tetralogy of Fallot is not known. However, some studies suggest that the disorder may be due to the interaction of several genetic and/or environmental factors (multifactorial). Therefore, researchers suspect that something may affect the genes in the developing fetus, causing this birth defect, but the exact nature of this trigger is not known.
Some conditions that may increase the risk of having a child with tetralogy of Fallot are viral illnesses, alcohol use, diabetes, poor nutrition, and being pregnant over the age of 40.
Approximately 25 percent of infants with tetralogy of Fallot also have other congenital birth defects that are not related to the function or structure of the heart.
Tetralogy of Fallot is a rare congenital malformation of the heart that occurs more frequently in males than females. Approximately 1 percent of newborns have congenital heart defects. About 10 percent of these infants are diagnosed with tetralogy of Fallot. This heart defect is usually detected weeks or months after birth. The prevalence of tetralogy of Fallot is estimated to be 1 in 3,000 live births.
Children with chromosome disorders, such as Down syndrome, often have tetralogy of Fallot and other congenital heart diseases.
Symptoms of the following disorders can be similar to those of tetralogy of Fallot. Comparisons may be useful for a differential diagnosis:
Atrial septal defects (ASDs) are common congenital heart defects characterized by the presence of a small opening between the two atria of the heart. These defects lead to an increase in the workload on the right side of the heart as well as excessive blood flow to the lungs. The symptoms, which vary greatly, may become apparent during infancy, childhood, or adulthood, depend on the severity of the defect. The symptoms tend to be mild at first and may include difficulty breathing (dyspnea), increased susceptibility to respiratory infections, and abnormal bluish discoloration of the skin and/or mucous membranes (cyanosis). Some people with ASDs may be at increased risk for the formation of blood clots that can travel to the major arteries (embolism), blocking blood circulation. (For more information on this disorder, choose “Atrial Septal Defect” as your search term in the Rare Disease Database.)
Ventricular septal defects (VSDs) are a group of common congenital heart defects characterized by the absence of one ventricle. Infants with these defects may have 2 atria and 1 large ventricle. Symptoms of these conditions are similar to those of other congenital heart defects and may include an abnormally rapid rate of breathing (tachypnea), blue color to the skin (cyanosis), wheezing, a rapid heart-beat (tachycardia), and/or an abnormally enlarged liver (hepatomegaly). VSDs can also cause the excessive accumulation of fluid around the heart, leading to congestive heart failure. (For more information on this disorder, choose “Ventricular Septal Defect” as your search term in the Rare Disease Database.)
Atrioventricular septal defect (AVSD) is a rare heart defect that is present at birth (congenital) and is characterized by the improper development of the septa and valves of the heart. Infants with the complete form of the defect usually develop congestive heart failure. Excessive fluid accumulates in other areas of the body, especially the lungs. Pulmonary congestion may lead to difficulty breathing (dyspnea). Other symptoms may include a bluish discoloration of the skin (cyanosis), poor feeding habits, abnormally rapid breathing (tachypnea) and heart rate (tachycardia), and/or excessive sweating (hyperhidrosis). Adults with AVSD may experience abnormally low blood pressure, irregular heartbeats, and/or a rapid heartbeat. (For more information on this disorder, choose “Atrioventricular Septal Defect” as your search term in the Rare Disease Database.)
Cor triatriatum is an extremely rare congenital heart defect characterized by the presence of an extra chamber above the left atrium of the heart. The pulmonary veins, returning blood from the lungs, drain into this extra “third atrium.” The symptoms of cor triatriatum vary greatly and depend on the size of the opening between the chambers. Symptoms may include abnormally rapid breathing (tachypnea), bluish discoloration to the skin (cyanosis), wheezing, coughing, and/or abnormal accumulation of fluid in the lungs (pulmonary congestion). (For more information on this disorder, choose “Cor Triatriatum” as your search term in the Rare Disease Database.)
Cor triloculare biatriatum is an extremely rare congenital heart defect characterized by the absence of one ventricle. Infants with this defect have 2 atria and 1 large ventricle. The symptoms are similar to those of other congenital heart defects and may include breathing difficulties (dyspnea), excessive accumulation of fluid in the lungs and around the heart (pulmonary edema), and/or a bluish discoloration of the skin and mucous membranes (cyanosis). Other symptoms may include poor feeding habits, abnormally rapid breathing (tachypnea), and/or an abnormally rapid heartbeat (tachycardia).
Mitral valve stenosis is a rare heart defect that may be present at birth (congenital) or acquired. It is characterized by the abnormal narrowing of the opening of the mitral valve. In the congenital form, the symptoms vary greatly and may include coughing, difficulty breathing, heart palpitations, and/or frequent respiratory infections. In acquired mitral valve stenosis, the symptoms may also include weakness, abdominal discomfort, chest pain (angina), and/or periodic loss of consciousness.
The diagnosis of tetralogy of Fallot is confirmed by clinical evaluation and physical examination. A variety of specialized tests including electrocardiogram, echocardiogram, and cardiac catheterization may be performed to aid in diagnosis and therapy. When tetralogy of Fallot is present, x-ray studies usually reveal a normal-sized heart that is characteristically boot-shaped (coeur en sabot). Periodic measurements of systemic blood oxygen saturation and hemoglobin are also advisable. Infants with this disorder usually have a relatively loud murmur over the upper left breastbone.
The definitive treatment for tetralogy of Fallot is surgery (i.e., Blalock-Taussig shunting procedure, aortic/pulmonary shunt, intracardiac repair, balloon pulmonary valvuloplasty and/or valve replacement). Surgical correction of this heart malformation is best accomplished during infancy. Selection of the exact surgical procedure is based on the severity of symptoms and extent of the malformation.
The surgeon will widen the pulmonary valve and the passage from the right ventricle to the pulmonary artery is enlarged. A patch covers the hole in the septum to repair the ventricular septal defect. By resolving the VSD and the pulmonary valve problems, it fixes the other two defects.
Temporary surgery may be recommended babies are too weak or small to have the full repair surgery; the full repair surgery will be performed when the baby is stronger. A tube or a “shunt” is placed between a large artery branching off the aorta and the pulmonary artery. It creates a pathway for blood to travel to the lungs to get oxygen. The tube is removed during the full repair surgery.
When early repair is not possible, other surgical measures may be taken during infancy or early childhood.
Prior to surgery, treatment to control symptoms (palliative) may include the maintenance of adequate fluid intake (hydration), monitoring of hemoglobin levels in the blood, and the avoidance of strenuous exercise. Heart medications (i.e., digitalis) may be prescribed to help control irregular heartbeats (arrhythmias), rapid heartbeats, and/or heart failure.
Episodes of severe symptoms or “blue spells” (hypoxia) may require the administration of supplemental oxygen, morphine, and/or other drugs that improve oxygen concentration. The knee-chest position may also bring some symptomatic relief. Sodium bicarbonate may be administered to lower abnormally high levels of acid in the blood (acidosis). The drug propranolol may be given to help prevent future spells and to reduce their severity. Drugs that help to remove excess fluid from the body (diuretics), dietary salt restriction, and bed rest may be effective in treating congestive heart failure.
Antibiotics may be prescribed to infants with tetralogy of Fallot to help prevent infections (prophylaxis) because children with this disorder are susceptible to bacterial infection of the heart (endocarditis). Respiratory infections must be treated vigorously and early. Children should be given antibiotics at times of predictable risk (e.g., tooth extractions and surgery). Other treatment is symptomatic and supportive.
Although the risk for tetralogy of Fallot in the siblings of infants with this disorder is thought to be very low, genetic counseling may be of benefit for parents and other family members.
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