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Summary Table

Category	Details
Risk Factors	Maternal diabetes, maternal alcohol use, maternal phenylketonuria, advanced maternal age, rubella infection during pregnancy. Strong association with 22q11.2 deletion (DiGeorge syndrome) and Down syndrome.
Etiology	Anterosuperior deviation of the infundibular (conal) septum during embryogenesis, leading to four anatomic features: pulmonary stenosis (RV outflow tract obstruction), overriding aorta, ventricular septal defect (VSD), and right ventricular hypertrophy.
Patient Presentation	Infant with cyanosis worsening with crying, feeding, or agitation; older child who squats during play to relieve breathlessness; "tet spells" (hypercyanotic episodes) with sudden deep cyanosis, irritability, and gasping respirations.
Classic Physical Exam	Harsh systolic ejection murmur at the left upper sternal border (from pulmonary stenosis, not the VSD), single loud S2, RV heave, clubbing in older unrepaired children, central cyanosis.
Key Diagnostic Results	CXR: boot-shaped heart (coeur en sabot) with decreased pulmonary vascular markings. ECG: right axis deviation and RV hypertrophy. Echocardiography is confirmatory.
Management	Acute tet spell: knee-to-chest position, oxygen, morphine, IV fluids, beta-blocker, phenylephrine. Definitive: complete surgical repair around 3 to 6 months of age (VSD closure plus RV outflow tract reconstruction).
Keywords	"Boot-shaped heart," "tet spell," "squatting," "single S2," "overriding aorta," "infundibular stenosis," "22q11.2 deletion," "coeur en sabot," "hypercyanotic spell."

1. Pathophysiology

The entire disease stems from a single embryologic error: anterosuperior malalignment of the infundibular septum. This one developmental misstep produces all four anatomic features simultaneously, which is why they cluster together as a tetrad.

The malaligned septum narrows the right ventricular outflow tract, producing pulmonary stenosis (the dominant lesion that determines severity). Because the septum fails to fuse properly with the rest of the interventricular septum, a large malalignment-type VSD is created. The aortic root, sitting astride this defect, becomes the overriding aorta, receiving blood from both ventricles. Finally, because the right ventricle must pump against the obstructed outflow tract, it undergoes compensatory right ventricular hypertrophy.

The clinical picture follows directly from the hemodynamics. Deoxygenated blood entering the right ventricle meets resistance at the obstructed pulmonary outflow, so it takes the path of least resistance: right-to-left shunting across the VSD into the overriding aorta. This deoxygenated blood enters the systemic circulation, producing cyanosis. The degree of cyanosis depends on the ratio between systemic vascular resistance (SVR) and pulmonary vascular resistance, more accurately the degree of RV outflow obstruction.

This ratio also explains the tet spell. When an infant cries, feeds, or defecates, two things happen: catecholamines cause infundibular spasm (worsening RV outflow obstruction), and SVR drops. Both changes increase right-to-left shunting, dumping more deoxygenated blood into the aorta and producing acute, profound cyanosis. Older children instinctively squat because squatting kinks the femoral arteries and raises SVR, which reverses the shunt direction and improves pulmonary blood flow. This squatting reflex is one of the most testable behavioral signs in pediatric cardiology.

The single S2 is also pathophysiologically logical. Because pulmonary blood flow is so reduced, the pulmonary component of S2 (P2) is soft or absent, leaving only the aortic component audible. The murmur itself comes from the pulmonary stenosis, not the VSD, because the VSD is so large and unrestrictive that no pressure gradient (and therefore no turbulent flow) is generated across it. Paradoxically, the worse the tet spell, the softer the murmur, because pulmonary blood flow drops so low that turbulence at the outflow tract diminishes.

2. Classification of Clinical Manifestation

Type	Hemodynamics	Clinical Picture	Timing of Presentation
Pink ToF	Mild pulmonary stenosis, predominantly left-to-right shunt	Acyanotic; resembles isolated VSD with murmur and possible heart failure signs	Often delayed; may present in infancy with murmur only
Blue ToF	Moderate pulmonary stenosis, balanced or right-to-left shunt	Cyanosis with crying or feeding, episodic tet spells, eventual clubbing	Within first few months of life
Severe Tet (Pulmonary Atresia variant)	Near-total or complete RV outflow obstruction	Ductal-dependent pulmonary circulation; profound cyanosis at birth as ductus arteriosus closes	Neonatal period (hours to days after birth)
Tet with Absent Pulmonary Valve	Free pulmonary regurgitation, dilated pulmonary arteries	Respiratory distress from airway compression, less cyanosis	Neonatal or early infancy

The age at presentation depends on the severity of pulmonary stenosis, not on the VSD or aorta. This is an important teaching point: a "pink tet" infant can deteriorate into cyanosis as the infundibulum hypertrophies over months.

3. Diagnostic Workup

Test	Purpose	Findings
Pulse oximetry (newborn screening)	Initial screen for cyanotic heart disease	Low SpO2, pre-ductal/post-ductal difference may be present
Chest X-ray	Initial imaging	Boot-shaped heart, decreased pulmonary vascularity, right aortic arch in 25% of cases
ECG	Initial cardiac assessment	Right axis deviation, right ventricular hypertrophy
Echocardiography	Confirmatory test (Gold Standard)	Visualizes all four anatomic features; quantifies RV outflow gradient
Hyperoxia test	Differentiates cardiac from pulmonary cyanosis	PaO2 fails to rise above 150 mmHg on 100% oxygen (positive for cyanotic heart disease)
Cardiac MRI/CT	Pre-surgical planning	Defines coronary anatomy, RV outflow geometry, branch pulmonary arteries
Cardiac catheterization	Reserved for unclear anatomy or interventional planning	Direct pressure and saturation measurements
Genetic testing (FISH for 22q11.2)	Identify associated syndromes	Confirms DiGeorge syndrome

The workup typically begins when a clinician notes cyanosis, a murmur, or a failed pulse oximetry screen in a newborn or young infant. The best initial test is chest X-ray and ECG, which raise suspicion through the boot-shaped silhouette, decreased pulmonary markings, and right ventricular hypertrophy pattern. Hyperoxia testing helps separate cyanotic congenital heart disease from primary pulmonary causes when the diagnosis is unclear; a PaO2 that fails to rise meaningfully on 100% oxygen points to a cardiac right-to-left shunt.

The definitive (most accurate) diagnostic test is transthoracic echocardiography. It directly visualizes the four anatomic components, measures the RV outflow tract gradient, evaluates the size of the pulmonary arteries, and identifies coexisting lesions such as a right aortic arch or coronary anomalies. Echocardiography ends the diagnostic question; cardiac MRI, CT, or catheterization are reserved for surgical planning when echo windows are insufficient or when coronary or pulmonary artery anatomy needs further definition.

The "next best step" logic in vignettes usually runs: cyanotic infant with murmur, then chest X-ray (boot-shaped heart), then echocardiography for confirmation. Picking catheterization as the first confirmatory test is a common distractor and is incorrect in modern practice.

4. Management & Treatment

Phase	Intervention	Mechanism
Tet spell, immediate	Knee-to-chest position (or have child squat)	Increases SVR, reduces right-to-left shunt
Tet spell, second-line	100% oxygen	Pulmonary vasodilation, raises arterial saturation
Tet spell, pharmacologic	Morphine 0.1 mg/kg IM/IV/SC	Reduces respiratory drive, calms infundibular spasm, sedates
Tet spell, volume	IV normal saline bolus 10 to 20 mL/kg	Increases preload, improves pulmonary blood flow
Tet spell, refractory	IV propranolol 0.05 to 0.1 mg/kg or esmolol infusion	Relieves infundibular spasm
Tet spell, severe	IV phenylephrine	Raises SVR pharmacologically
Neonatal severe Tet (ductal-dependent)	Prostaglandin E1 infusion 0.05 to 0.1 mcg/kg/min	Maintains ductus arteriosus patency for pulmonary blood flow
Bridge therapy	Modified Blalock-Taussig-Thomas shunt	Provides systemic-to-pulmonary blood flow when complete repair is delayed
Definitive treatment	Complete intracardiac repair at 3 to 6 months of age	VSD patch closure + RV outflow tract reconstruction (transannular patch or valve-sparing)
Long-term follow-up	Lifelong cardiology surveillance	Monitor for pulmonary regurgitation, RV dilation, arrhythmia

Acute management of a tet spell must be reflexive.

The first move is to place the child in knee-to-chest position or instruct an older child to squat; this single mechanical maneuver raises systemic vascular resistance and often aborts the spell.
Oxygen is given simultaneously.
Morphine is the classic pharmacologic first step, calming the child and reducing infundibular spasm.
IV fluid bolus increases right ventricular preload and pushes more blood across the obstructed outflow into the lungs.
Beta-blockade with propranolol or esmolol relaxes the spastic infundibulum.
Phenylephrine is reserved for refractory cases to pharmacologically elevate SVR.

Inotropes such as dopamine or epinephrine are contraindicated in tet spells because they worsen infundibular contraction and deepen the obstruction.

For a neonate with severe disease (pulmonary atresia variant), pulmonary blood flow depends on the patent ductus arteriosus. Prostaglandin E1 must be started immediately to keep the ductus open as a bridge to surgery. Failure to recognize ductal-dependent circulation and stopping prostaglandin is a fatal error tested frequently.

The definitive treatment is complete surgical repair, generally performed between 3 and 6 months of age when the infant is symptomatic, or by 6 to 12 months even in stable cases. The operation closes the VSD with a patch and relieves RV outflow obstruction, often using a transannular patch when the pulmonary valve annulus is hypoplastic. A modified Blalock-Taussig-Thomas shunt (a Gore-Tex conduit between the subclavian and pulmonary artery) is now reserved for neonates too unstable or too small for primary repair, serving as a temporizing measure.

Long-term management focuses on the late complications of repair, principally pulmonary regurgitation, right ventricular dilation, and ventricular arrhythmias. Adult survivors require lifelong cardiology follow-up and may eventually need pulmonary valve replacement.

5. Differential Diagnosis & Distractors

Differential	Why It's Similar	Key Discriminator
Transposition of the Great Arteries	Cyanotic newborn, ductal-dependent	Presents with cyanosis at birth (hours of life); CXR shows "egg on a string" narrow mediastinum, increased pulmonary vascularity; usually no murmur
Tricuspid Atresia	Cyanotic infant with VSD physiology	ECG shows left axis deviation and LV hypertrophy (opposite of Tetralogy); single S2 also present but axis is the giveaway
Truncus Arteriosus	Cyanosis, single S2, VSD	Single arterial trunk on echo; CXR shows increased pulmonary vascularity; signs of heart failure dominate over cyanosis
Total Anomalous Pulmonary Venous Return	Cyanotic newborn	CXR shows "snowman" or figure-of-8 silhouette with increased pulmonary vascularity, often pulmonary edema
Eisenmenger Syndrome	Cyanosis with VSD	Occurs late in unrepaired left-to-right shunts; murmur softens as shunt reverses; not seen in infancy
Pulmonary Stenosis (isolated)	Similar systolic ejection murmur at LUSB	No cyanosis because there is no VSD for right-to-left shunting
Ventricular Septal Defect (isolated)	Similar VSD on echo	Holosystolic murmur, not ejection murmur; no cyanosis; increased pulmonary vascularity on CXR
Ebstein Anomaly	Cyanosis in newborn	Tricuspid valve displaced apically, massive right atrium, "wall-to-wall heart" on CXR; history of maternal lithium use

The most testable contrast is between Tetralogy of Fallot and Transposition of the Great Arteries. Both produce cyanotic newborns, but transposition presents within the first hours of life with profound cyanosis and minimal murmur, while Tetralogy classically presents over weeks to months with cyanosis triggered by exertion and a prominent murmur. The chest X-ray patterns ("boot" versus "egg on a string") and pulmonary vascularity (decreased versus increased) are decisive.

6. Traps & High-Yield Pearls

The most common way students miss this diagnosis is by misattributing the murmur. They hear "VSD" in the stem and choose isolated VSD, forgetting that the murmur of Tetralogy comes from the pulmonary stenosis, not the VSD, and that an unrestrictive VSD produces no murmur. A second classic trap: the question describes a child who squats during play, and students chase exotic answers when the squatting reflex is essentially pathognomonic for unrepaired Tetralogy.

The third trap is the tet spell management sequence. Students reach for inotropes (dopamine, epinephrine) to "help the heart," but these worsen infundibular spasm and deepen the shunt. The correct sequence is mechanical (knee-to-chest), then oxygen, morphine, fluids, beta-blocker, phenylephrine. The fourth trap is forgetting prostaglandin E1 in the ductal-dependent neonate; stopping prostaglandin in a cyanotic newborn before defining the anatomy can be lethal.

A fifth high-yield association is 22q11.2 deletion (DiGeorge syndrome). A vignette pairing congenital heart disease with hypocalcemic seizures, absent thymus, recurrent infections, or characteristic facies is pointing to DiGeorge, and Tetralogy is the most common cardiac lesion in this syndrome. Test writers love this combination.

Finally, recognize the "paradoxically softer murmur during a tet spell." Counterintuitively, when cyanosis worsens, the murmur diminishes because pulmonary blood flow drops so low that almost nothing crosses the outflow tract to generate turbulence. A vignette describing a cyanotic, gasping child whose murmur has become quieter is describing an active tet spell, not an improving patient.

The core competency tested is integrating embryology, hemodynamics, and bedside findings into a single coherent picture: one developmental error produces four anatomic features, which produce one shunt direction, which produces every clinical sign in the vignette. Mastery of Tetralogy is mastery of how to think about congenital heart disease as a whole.

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