Tetralogy of Fallot is most often diagnosed in the first few weeks of life due to either a loud murmur or cyanosis. Babies with tetralogy of Fallot usually have a patent ductus arteriosus at birth that provides additional blood flow to the lungs, so severe cyanosis is rare early after birth.

As the ductus arteriosus closes, which it typically will in the first days of life, cyanosis can develop or become more severe.

The degree of cyanosis is proportional to lung blood flow and thus depends upon the degree of narrowing of the outflow tract to the pulmonary arteries.

Rapid breathing in response to low oxygen levels and reduced pulmonary blood flow can occur. The heart murmur, which is commonly loud and harsh, is often absent in the first few days of life.

The arterial oxygen saturation of babies with tetralogy of Fallot can suddenly drop markedly. This phenomenon, called a "tetralogy spell," usually results from a sudden increased constriction of the outflow tract to the lungs so that pulmonary blood flow is further restricted. The lips and skin of babies who have a sudden decrease in arterial oxygen level will appear acutely more blue.

Children having a tetralogy spell will initially become extremely irritable in response to the critically low oxygen levels, and they may become sleepy or unresponsive if the severe cyanosis persists.

A tetralogy spell can sometimes be treated by comforting the infant and flexing the knees forward and upward. Most often, however, immediate medical attention is necessary.