Tetralogy of Fallot
Open accessAbstract
Tetralogy of Fallot is a congenital cardiac malformation that consists of an interventricular communication, also known as a ventricular septal defect, obstruction of the right ventricular outflow tract, override of the ventricular septum by the aortic root, and right ventricular hypertrophy. This combination of lesions occurs in 3 of every 10,000 live births, and accounts for 7-10% of all congenital cardiac malformations. Patients nowadays usually present as neonates, with cyanosis of varying intensity based on the degree of obstruction to flow of blood to the lungs. The aetiology is multifactorial, but reported associations include untreated maternal diabetes, phenylketonuria, and intake of retinoic acid. Associated chromosomal anomalies can include trisomies 21, 18, and 13, but recent experience points to the much more frequent association of microdeletions of chromosome 22. The risk of recurrence in families is 3%. Useful diagnostic tests are the chest radiograph, electrocardiogram, and echocardiogram. The echocardiogram establishes the definitive diagnosis, and usually provides sufficient information for planning of treatment, which is surgical. Approximately half of patients are now diagnosed antenatally. Differential diagnosis includes primary pulmonary causes of cyanosis, along with other cyanotic heart lesions, such as critical pulmonary stenosis and transposed arterial trunks. Neonates who present with ductal-dependent flow to the lungs will receive prostaglandins to maintain ductal patency until surgical intervention is performed. Initial intervention may be palliative, such as surgical creation of a systemic-to-pulmonary arterial shunt, but the trend in centres of excellence is increasingly towards neonatal complete repair. Centres that undertake neonatal palliation will perform the complete repair at the age of 4 to 6 months. Follow-up in patients born 30 years ago shows a rate of survival greater than 85%. Chronic issues that now face such adults include pulmonary regurgitation, recurrence of pulmonary stenosis, and ventricular arrhythmias. As the strategies for surgical and medical management have progressed, the morbidity and mortality of those born with tetralogy of Fallot in the current era is expected to be significantly improved.
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This single lesion is responsible for all the main components of the disease: a <50% override of the aorta over the muscular ventricular septum, muscular obstruction of the RVOT, and right ventricle hypertrophy (RVH).
“This single lesion is responsible for all the main components of the disease: a <50% override of the aorta over the muscular ventricular septum, muscular obstruction of the RVOT, and right ventricle hypertrophy (RVH) [6].”
From Multimodality imaging assessment of tetralogy of Fallot: From diagnosis to long-term follow-up (2023) · cites this paper as [6]
The Anatomy section says deviation of the outlet septum produces aortic override and contributes to right ventricular hypertrophy. It also says right ventricular outflow tract obstruction requires abnormal septoparietal trabeculations in addition to that deviation, so a single lesion does not account for all the components listed. The Override of the aorta section describes override but gives no <50% threshold. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the United States, Tetralogy of Fallot birth prevalence is 3.9 per 10,000 live births, with about 1,660 babies born with Tetralogy of Fallot annually, and Tetralogy of Fallot represents approximately 6.7% of all congenital heart defects.
“Developed countries like the United States (US) reported a birth prevalence of 3.9 per 10,000 live births, with an estimated 1,660 babies born with TOF each year [2, 11]. In the US, TOF also represents approximately 6.7% of all CHDs [2].”
From Pooled prevalence and subgroup variations of Tetralogy of Fallot among children and adolescents with congenital heart defect in Sub-Saharan Africa: A systematic review and meta-analysis (2025) · cites this paper as [11]
The Epidemiology section reports Tetralogy of Fallot in 3 per 10,000 live births and up to one-tenth of congenital cardiac lesions; the Abstract gives 7–10% of congenital cardiac malformations. These passages support the general prevalence context, but not the cited US-specific figures of 3.9 per 10,000, approximately 1,660 births annually, or 6.7% of congenital heart defects. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe typical VSD in TOF is an anterior malalignment type of outlet VSD, with the conal septum anteriorly diverging from the muscular septum.
“Even though several anatomical types of VSD have been described, the typical VSD in TOF is an anterior malalignment type of outlet VSD, with the conal septum anteriorly diverging from the muscular septum.”
From Multimodality imaging assessment of tetralogy of Fallot: From diagnosis to long-term follow-up (2023) · cites this paper as [6]
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- Authors
- Bailliard, F., & Anderson, R. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Anderson, Robert H
- Venue
- Orphanet Journal of Rare Diseases
- Published
- 2009-01-13
- Volume
- 4
- Issue
- 1
- Pages
- 2-2
- ISSN
- 1750-1172 (ISSN-L)
- PMC
- PMC2651859
- OpenAlex
- W3204567248
- Cited by
- 345
- References
- 42
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 31 · 2023: 44 · 2022: 26 · 2021: 22 · 2020: 24 · 2019: 25 · 2018: 16 · 2017: 13 · 2016: 19 · 2015: 16 · 2014: 10 · 2013: 11 · 2012: 12
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiovascular Conditions and Treatments
- Keywords
- tetralogy of Fallot, congenital heart disease, ventricular septal defect, right ventricular outflow tract obstruction, cyanosis, prenatal diagnosis, echocardiography, neonatal palliation, prostaglandin E2, systemic-to-pulmonary shunt, pulmonary regurgitation, ventricular arrhythmias, adult congenital heart disease, Down syndrome, trisomy 18, trisomy 13, phenylketonuria, maternal diabetes, retinoic acid
- MeSH terms
- Adult, Genetic Counseling, Heart Defects, Congenital, Humans, Infant, Infant, Newborn, Prognosis, Tetralogy of Fallot, Ultrasonography
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