Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect, characterized by four structural abnormalities of the heart: a ventricular septal defect (VSD, a hole between the lower chambers of the heart), overriding aorta (the aorta is positioned over the VSD rather than solely over the left ventricle), right ventricular outflow tract obstruction (RVOTO, narrowing at or near the pulmonary valve that restricts blood flow to the lungs), and right ventricular hypertrophy (thickening of the right ventricle's muscular wall as a consequence of the obstruction). These defects result in oxygen-poor blood being pumped to the body, leading to cyanosis — a bluish discoloration of the skin, lips, and nail beds. TOF is typically diagnosed in the neonatal period or early infancy, often presenting with cyanosis, heart murmurs, and episodes called "tet spells" (hypercyanotic spells), during which the infant becomes suddenly very blue, irritable, and may lose consciousness due to a rapid drop in blood oxygen levels. Feeding difficulties, poor weight gain, and exercise intolerance may also be observed. The severity of symptoms depends largely on the degree of right ventricular outflow tract obstruction; some patients with milder obstruction may initially appear "pink" and present later in infancy. TOF can occur as an isolated cardiac malformation or as part of broader genetic syndromes, including 22q11.2 deletion syndrome (DiGeorge syndrome), trisomy 21 (Down syndrome), and Alagille syndrome. Several genes have been implicated, including NKX2-5, JAG1, TBX1, GATA4, and FOXC2, among others. The condition is treated surgically, with complete intracardiac repair typically performed in the first year of life. This surgery involves closure of the VSD and relief of the right ventricular outflow tract obstruction. Prior to definitive repair, severely cyanotic neonates may require a palliative shunt procedure (such as a Blalock-Taussig shunt) or prostaglandin infusion to maintain blood flow to the lungs. With modern surgical techniques, long-term survival is excellent, though patients require lifelong cardiac follow-up for potential complications including pulmonary regurgitation, arrhythmias, right ventricular dysfunction, and the possible need for pulmonary valve replacement later in life.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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