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.
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 case to case. 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. 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 and then extremely cyanotic while gasping for air. 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).
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.
Researchers determined that some cases of tetralogy of Fallot may occur, in part, because of disruption or changes (mutations) of a gene located on the short arm (p) of chromosome 20 (20p12). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 20p12” refers to band 12 on the short arm of chromosome 20. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Researchers have determined that some cases of tetralogy of Fallot may occur, in part, because of disruption or changes (mutations) of a gene located on the long arm (q) of chromosome 5 (5q34).
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 may also occur as part of a larger disorder such as velocardiofacial syndrome, chromosome 14, trisomy mosaic, Goldenhar syndrome or fetal retinoid syndrome.
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.
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. When early repair is not possible, other surgical measures may be taken during infancy or early childhood. A "shunt" or tube may be constructed between the aorta and the pulmonary vessels.
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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Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1308.
Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1311-15.
Braunwald E, ed. Heart Disease. A Textbook of Cardiovascular Medicine. 3rd ed. Philadelphia, PA: W. B. Saunders Company; 1988:946-8, 988-91.
Therrien J, et al. A pilot study of exercise training in adult patients with repaired tetralogy of Fallot. Can J Cardiol. 2003;19:685-89.
Walker WT, et al. Quality of life after repair of tetralogy of Fallot. Cardiol Young. 2002;12:549-53.
Mulder TJ, et al. A multicenter analysis of the choice of initial surgical procedure in tetralogy of Fallot. Pediatr Cardiol. 2002;23:580-86.
Eldadah ZA, et al. Familial tetralogy of Fallot caused by mutation in the jagged1 gene. Hum Mol Genet. 2001;10:163-69.
Goldmuntz E, et al. NKX2.5 mutations in patients with tetralogy of Fallot. Circulation. 2001;104:2565-68.
Digilio MC, et al. Recurrence risk figures for isolated tetralogy of Fallot after screening 22q11 microdeletion. J Med Genet. 1997;34:188-90.
Santoro G, et al. Echocardiographically guided repair of tetralogy of Fallot. Am J Cardiol. 1994;73:808-11.
Sousa Uva M, et al. Surgery for tetralogy of Fallot at less than six months of age. J Thorac Cardiovasc Surg. 1994;107:1291-300.
Yamagishi M, et al. Outflow reconstruction of tetralogy of Fallot using a Gore-Tex valve. Ann Thorac Surg. 1993;56:1416-17.
Heinemann MK, et al. Preoperative management of neonatal tetralogy of Fallot with absent pulmonary valve syndrome. Thorac Surg. 1993;55:172-74.
Murphy JG, et al. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med. 1993;329:593- 99.
Warnes CA., Tetralogy of Fallot and pulmonary atresia/ventricular septal defect. Cardiol Clin. 1993;11:643-50.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:187500; Last Update:4/29/02.
Pflieger K, eMedicine. Last Updated: August 29, 2001. 11pp.
Cincinnati’s Children’s Hospital Medical Center. The Heart Center Encyclopedia. Tetralogy of Fallot.
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