History and exam

Key diagnostic factors

common

hypercyanotic episodes

Hypercyanotic (tet) spells may present as episodic, increasing cyanosis in a baby with TOF.

The baby is typically crying and breathing deeply and rapidly, but may not be in significant respiratory distress.

The typical murmur of TOF may disappear during the spell.

This presentation is potentially life-threatening and requires rapid intervention

Can occur in both cyanotic and acyanotic infants with TOF.

harsh systolic ejection murmur

Loudest at the left sternal border represents the blood flow across the narrowed right ventricular outflow tract.

cyanosis

Usually noted; however, the degree of cyanosis may vary and can be subtle. TOF with severe pulmonary obstruction is a more severe presentation and may present in a newborn who appears severely cyanotic at birth.

tachypnea

May have significant tachypnea with severe pulmonary obstruction.

Other diagnostic factors

uncommon

shock

Infants with severe pulmonary obstruction or a hypercyanotic spell may present with severe cyanosis and acidosis due to tissue hypoxia.

Risk factors

weak

trisomy 21, 18, or 13

There is a well-accepted association between certain genetic defects and congenital heart disease. Patients with trisomy 21, 18, or 13 have a higher incidence of TOF than infants without trisomy.[7]

chromosome 22q11 deletions (DiGeorge syndrome)

A retrospective analysis in patients with apparently nonsyndromic TOF found 10 out of 21 patients to have deletions of chromosome 22q11 (DiGeorge and associated syndromes), suggesting a region on this chromosome may harbor a TOF susceptibility gene.[8]

Jagged1 gene mutations (Alagille syndrome)

Alagille syndrome, a syndrome with cardiovascular phenotypes ranging from mild pulmonic stenosis to TOF with severe pulmonary obstruction, has been found to be due to mutations in the Jagged1 gene.[10] Additionally, mutations in Jagged1 have been associated with nonsyndromic forms of TOF.[11]

mutation in NKX2.5 gene

A prospective study looking for mutations in NKX2.5 in patients with known TOF found approximately 4% of patients with nonsyndromic TOF to have a mutation in NKX2.5.[12]

environmental factors

Increasing evidence suggests environmental factors, such as maternal diabetes and phenylketonuria and maternal ingestion of retinoic acids and trimethadione, may play a significant causative role in certain cases of congenital heart disease.[14][15][16]

family history of congenital heart disease

Believed to contribute to the recurrence of congenital heart disease in a family, but it cannot be clearly explained by mendelian genetics or complete penetrance.[6]

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