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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Pediatric Cardiology

Understanding Tetralogy of Fallot: Basics, Anatomy, and Causes

At a Glance

Tetralogy of Fallot (ToF) is a congenital heart condition involving four specific structural defects that reduce blood oxygen levels. While it can cause cyanosis (a blue skin tint) and "tet spells," it is a well-understood condition that can be effectively managed and treated with surgery.

Learning that your child has a heart condition can feel overwhelming. Tetralogy of Fallot (ToF) is a complex but well-understood condition that affects how blood flows through the heart and to the rest of the body [1]. It is the most common “cyanotic” heart defect, meaning it can cause a bluish tint to the skin because the body isn’t getting enough oxygen [2].

While it is a serious diagnosis, advancements in surgery and care mean that most children born with ToF grow up to lead active, healthy lives.

The Four Heart Differences

The name “Tetralogy” comes from the Greek word for four, representing the four specific structural differences in the heart that occur together [1][3]:

  1. Ventricular Septal Defect (VSD): This is a hole in the wall (septum) that separates the two bottom chambers of the heart (the ventricles) [1]. This hole allows oxygen-rich blood and oxygen-poor blood to mix [4].
  2. Pulmonary Stenosis: This is a narrowing of the exit from the right ventricle. It may involve the pulmonary valve (the door to the lungs) or the passage leading to it [5]. This narrowing makes it harder for the heart to pump blood into the lungs to get oxygen [6].
  3. Overriding Aorta: In a typical heart, the aorta (the main artery to the body) sits over the left ventricle. In ToF, the aorta is shifted and sits directly over the VSD [1]. This means it picks up a mix of both oxygen-rich and oxygen-poor blood to send to the body [1].
  4. Right Ventricular Hypertrophy: Because the right ventricle has to work much harder to push blood through the narrow pulmonary exit, the muscle becomes thickened and enlarged over time [7][8].

When discussing these defects with your doctor, ask them to point out your child’s specific anatomy on a diagram. Visualizing the differences can make it much easier to understand.

Why the Body Turns Blue: The “Shunt”

In a typical heart, the right side pumps blood to the lungs, and the left side pumps blood to the rest of the body. In ToF, the narrowing in the pulmonary exit (stenosis) acts like a “dam” [5].

Because it is so hard for blood to get through that “dam” to the lungs, it takes the path of least resistance. It flows through the VSD hole from the right side directly into the left side [5][9]. This is called a right-to-left shunt. This deoxygenated (purple) blood then enters the aorta and circulates through the body, which can lead to cyanosis—a bluish tint to the lips, skin, or fingernails [10][11].

Understanding “Tet Spells”

Sometimes, the “dam” (the pulmonary narrowing) can tighten suddenly, or the pressure in the body can drop, forcing even more blood through the VSD and away from the lungs [10]. This causes a sudden drop in oxygen levels called a hypercyanotic spell or “tet spell” [6]. These are often triggered by crying, feeding, or bowel movements [10]. You can learn more about how to manage these in the Symptoms and Tet Spells section.

What Causes Tetralogy of Fallot?

ToF occurs early in pregnancy when the baby’s heart is still forming. While we don’t always know why it happens, research has identified several factors that may play a role.

Genetic Links

Many cases of ToF are linked to changes in genes that guide heart development [12][13].

  • 22q11.2 Deletion Syndrome: About 15% of children with ToF have a genetic condition called 22q11.2 deletion syndrome (also known as DiGeorge syndrome) [14][15]. This is a tiny missing piece of chromosome 22 [16].
  • Other Genes: Other specific genes (such as GATA4, NKX2.5, and JAG1) have also been linked to the development of ToF [17][12].

Because of these links, doctors often recommend genetic testing (like a chromosomal microarray) for babies diagnosed with ToF to help provide the best possible care plan [18][19].

Environmental Factors

Some studies suggest that environmental factors during pregnancy might increase the risk, such as maternal exposure to passive smoking or certain chemicals [20][21]. However, in most cases, ToF is a random occurrence. It is important for parents to know that they did nothing to cause it.

How Common Is It?

ToF is the most common form of cyanotic heart disease [2]. It is a “conotruncal” defect, meaning it affects the part of the heart where the main large blood vessels are formed. While it is a complex condition, it is a “classic” heart defect that pediatric cardiologists and surgeons are very experienced in treating.

Common questions in this guide

What are the four heart defects in Tetralogy of Fallot?
The four structural differences are a ventricular septal defect (a hole between the lower heart chambers), pulmonary stenosis (a narrowed exit to the lungs), an overriding aorta, and a thickened right ventricle muscle.
Why does Tetralogy of Fallot cause a blue skin tint?
The narrowing in the pathway to the lungs forces oxygen-poor blood to bypass the lungs and circulate directly to the body. This lack of oxygen causes the skin, lips, or fingernails to look blue, a condition known as cyanosis.
What is a 'tet spell'?
A tet spell, or hypercyanotic spell, is a sudden, dangerous drop in blood oxygen levels. It happens when the pathway to the lungs temporarily tightens, forcing blood away from the lungs, and is often triggered by crying, feeding, or bowel movements.
Are there genetic causes for Tetralogy of Fallot?
Yes, many cases of ToF are linked to genetic changes that affect heart development, such as 22q11.2 deletion syndrome (DiGeorge syndrome). Because of this link, doctors often recommend genetic testing to help tailor the best care plan for your child.
Did I do something during pregnancy to cause my baby's Tetralogy of Fallot?
In most cases, Tetralogy of Fallot happens randomly while the baby's heart is forming early in pregnancy. While certain environmental factors may play a small role, it is important for parents to know that they did nothing to cause the condition.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Can you show me on a diagram exactly where my child's VSD is and how severe the pulmonary stenosis is?
  2. 2.Given the link between ToF and genetic syndromes, should my child have a chromosomal microarray test for 22q11.2 deletion?
  3. 3.How does the degree of pulmonary stenosis in my child affect the timing of their first surgery?
  4. 4.What signs of a 'tet spell' should I look for, and exactly what steps should I take if one happens?
  5. 5.Does my child have any other heart or vessel variations, like a right-sided aortic arch, that we should know about?

Questions For You

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References

References (21)
  1. 1

    Cardiovascular imaging approach in pre and postoperative tetralogy of Fallot.

    Apostolopoulou SC, Manginas A, Kelekis NL, Noutsias M

    BMC cardiovascular disorders 2019; (19(1)):7 doi:10.1186/s12872-018-0996-9.

    PMID: 30616556
  2. 2

    The Needle in the Haystack-Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot.

    Grunert M, Appelt S, Grossfeld P, Sperling SR

    Journal of cardiovascular development and disease 2020; (7(4)) doi:10.3390/jcdd7040055.

    PMID: 33276527
  3. 3

    Clinical Presentation and Therapy of Tetralogy of Fallot and Double-Outlet Right Ventricle.

    Haas NA, Driscoll DJ, Rickert-Sperling S

    Advances in experimental medicine and biology 2024; (1441()):617-627 doi:10.1007/978-3-031-44087-8_35.

    PMID: 38884737
  4. 4

    A Comprehensive Review of Canine and Feline Ventricular Septal Defects-From Pathogenesis to Long-Term Follow-Up.

    Graczyk S, Grzeczka A, Pasławska U

    Animals : an open access journal from MDPI 2025; (15(6)) doi:10.3390/ani15060850.

    PMID: 40150379
  5. 5

    Multi-detector computed tomography angiographic evaluation of right ventricular outflow tract obstruction and other associated cardiovascular anomalies in tetralogy of Fallot patients.

    Singh RKR, Jain N, Kumar S, Garg N

    Polish journal of radiology 2019; (84()):e511-e516 doi:10.5114/pjr.2019.91203.

    PMID: 32082448
  6. 6

    Tetralogy of Fallot: Everything you wanted to know but were afraid to ask.

    Wise-Faberowski L, Asija R, McElhinney DB

    Paediatric anaesthesia 2019; (29(5)):475-482 doi:10.1111/pan.13569.

    PMID: 30592107
  7. 7

    [Multimodality imaging of adult patients with surgically corrected tetralogy of Fallot. Results from the CSONGRAD Registry]

    Rácz G, Zagyi A, Tóth A, et al.

    Orvosi hetilap 2023; (164(5)):186-194 doi:10.1556/650.2023.32696.

    PMID: 36739548
  8. 8

    Histopathology of the right ventricular outflow tract and the relation to hemodynamics in patients with repaired tetralogy of Fallot.

    Chowdhury UK, Jha A, Ray R, et al.

    The Journal of thoracic and cardiovascular surgery 2019; (158(4)):1173-1183.e5 doi:10.1016/j.jtcvs.2019.03.118.

    PMID: 31133352
  9. 9

    Unrepaired tetralogy of Fallot in a 58-year-old female: factors contributing to the observed survival (case report).

    Elouardi A, Messouak M

    The Pan African medical journal 2023; (45()):154 doi:10.11604/pamj.2023.45.154.29477.

    PMID: 37869227
  10. 10

    Unrepaired tetralogy of Fallot in the adult: an unexpected diagnosis.

    Garcia Brás P, Branco Mano T, Sousa L

    Cardiology in the young 2023; (33(2)):323-324 doi:10.1017/S1047951122001779.

    PMID: 35730183
  11. 11

    Diagnosis and treatment of adults with congenital heart disease.

    Henning RJ

    Future cardiology 2020; (16(4)):317-342 doi:10.2217/fca-2019-0061.

    PMID: 32297523
  12. 12

    Genetic Origins of Tetralogy of Fallot.

    Morgenthau A, Frishman WH

    Cardiology in review 2018; (26(2)):86-92 doi:10.1097/CRD.0000000000000170.

    PMID: 29045289
  13. 13

    Whole exome sequencing identifies novel inherited genetic variants in tetralogy of Fallot.

    Pan Y, Liu M, Zhang S, et al.

    Journal of thoracic disease 2022; (14(8)):3008-3015 doi:10.21037/jtd-22-970.

    PMID: 36071769
  14. 14

    Surgical Outcomes in Syndromic Tetralogy of Fallot: A Systematic Review and Evidence Quality Assessment.

    Athanasiadis DI, Mylonas KS, Kasparian K, et al.

    Pediatric cardiology 2019; (40(6)):1105-1112 doi:10.1007/s00246-019-02133-z.

    PMID: 31214731
  15. 15

    22q11.2 Deletion Syndrome: Impact of Genetics in the Treatment of Conotruncal Heart Defects.

    Putotto C, Pugnaloni F, Unolt M, et al.

    Children (Basel, Switzerland) 2022; (9(6)) doi:10.3390/children9060772.

    PMID: 35740709
  16. 16

    Delineation of a recognizable phenotype for the recurrent LCR22-C to D/E atypical 22q11.2 deletion.

    Bengoa-Alonso A, Artigas-López M, Moreno-Igoa M, et al.

    American journal of medical genetics. Part A 2016; (170(6)):1485-94 doi:10.1002/ajmg.a.37614.

    PMID: 26991864
  17. 17

    A novel heterozygous pathogenic variant in HEY2 led to a familial form of non-syndromic Tetralogy of Fallot.

    Bergès C, Laffargue F, Dauphin C, et al.

    European journal of human genetics : EJHG 2025; (33(8)):1072-1075 doi:10.1038/s41431-025-01880-3.

    PMID: 40481234
  18. 18

    Genetic anomalies in fetuses with tetralogy of Fallot by using high-definition chromosomal microarray analysis.

    Peng R, Zheng J, Xie HN, et al.

    Cardiovascular ultrasound 2019; (17(1)):8 doi:10.1186/s12947-019-0159-x.

    PMID: 31060568
  19. 19

    22q11.2 deletion syndrome and congenital heart disease.

    Goldmuntz E

    American journal of medical genetics. Part C, Seminars in medical genetics 2020; (184(1)):64-72 doi:10.1002/ajmg.c.31774.

    PMID: 32049433
  20. 20

    GATA4 molecular screening and assessment of environmental risk factors in a Moroccan cohort with tetralogy of Fallot.

    El Bouchikhi I, Belhassan K, Moufid FZ, et al.

    African health sciences 2018; (18(4)):922-930 doi:10.4314/ahs.v18i4.11.

    PMID: 30766556
  21. 21

    Maternal occupational exposure to polycyclic aromatic hydrocarbons and the risk of isolated congenital heart defects among offspring.

    Patel J, Nembhard WN, Politis MD, et al.

    Environmental research 2020; (186()):109550 doi:10.1016/j.envres.2020.109550.

    PMID: 32335433

This page provides basic educational information about Tetralogy of Fallot anatomy and causes. It is not a substitute for professional medical advice, diagnosis, or treatment from a qualified pediatric cardiologist.

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