Details of Disease

Disease Name

Tetralogy of fallot

Fallot tetralogy; TOF; tetralogy of FALLOT; tetralogy of fallot; ventricular septal defect with pulmonary stenosis or atresia, dextraposition of aorta, and hypertrophy of right ventricle

Definition

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.

Disease Hierarchy

DISMT2VZ: Cardiogenetic disease

DIS7FMIG: Conotruncal heart malformations

DISQBA23: Congenital heart disease

DISMHFNW: Tetralogy of fallot

Disease Identifiers

MONDO ID

MONDO_0008542

MESH ID

D013771

UMLS CUI

C0039685

OMIM ID

187500

MedGen ID

21498

HPO ID

HP:0001636

Orphanet ID

3303

SNOMED CT ID

86299006

General Information of Disease (ID: DISMHFNW)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alprostadil	DMWH7NQ	Approved	Small molecular drug	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 53 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ZFPM2	OTBBEWEO	Strong	Autosomal dominant	[2]
BVES	OT4GT1WC	Limited	Autosomal recessive	[2]
GDF1	OTZ1VRBH	Limited	Autosomal dominant	[20]
GPC5	OT8NR7GC	Limited	Genetic Variation	[8]
NAA25	OTS3QVF1	Limited	Genetic Variation	[8]
PITX2	OTWMXAOY	Limited	Biomarker	[21]
PVR	OT3N91T7	Limited	Biomarker	[22]
TAB2	OTPZK76F	Limited	Biomarker	[23]
TPM1	OTD73X6R	Limited	Genetic Variation	[24]
FLT4	OTRAA26B	Supportive	Autosomal dominant	[9]
GATA4	OTQHWAZG	Supportive	Autosomal dominant	[10]
GATA5	OTO81B63	Supportive	Autosomal dominant	[25]
JAG1	OT3LGT6K	Supportive	Autosomal dominant	[26]
AATF	OT1QOKLD	moderate	Biomarker	[27]
ACSM3	OT0AE1IV	moderate	Biomarker	[28]
ACTC1	OTJU04B1	moderate	Biomarker	[29]
CHD1L	OT7CZK7C	moderate	Biomarker	[30]
CHMP5	OTQWZL6R	moderate	Biomarker	[31]
CORO7	OTG7MEAJ	moderate	Altered Expression	[32]
DNTT	OTFSEF12	moderate	Biomarker	[33]
DVL2	OTMNYNCM	moderate	Biomarker	[34]
FEZF2	OTU4TXIW	moderate	Biomarker	[35]
FOXH1	OTEXJ9SL	moderate	Biomarker	[11]
GATA6	OTO2BC0F	Moderate	Autosomal dominant	[2]
HAND2	OTCXYW4Y	moderate	Genetic Variation	[36]
JARID2	OT14UM8H	moderate	Biomarker	[37]
MAVS	OTTQ0J64	moderate	Biomarker	[38]
MBNL1	OTOV7J85	moderate	Altered Expression	[12]
MEIS2	OTG4ADLM	moderate	Biomarker	[29]
MYL4	OTURFCSE	moderate	Biomarker	[30]
NKX2-6	OTPPKGTE	moderate	SusceptibilityMutation	[39]
PBX3	OT8WMVM4	moderate	Biomarker	[40]
TADA2A	OTXUMEL9	moderate	Genetic Variation	[27]
TFAP2B	OTR1T8E9	moderate	Genetic Variation	[41]
TFAP2C	OTUDIW05	moderate	Altered Expression	[42]
CD48	OT83ZNPP	Strong	Genetic Variation	[26]
CITED2	OT812TV7	Strong	Genetic Variation	[43]
CRKL	OTOYSD1R	Strong	Biomarker	[44]
DGCR8	OT62LXE4	Strong	Altered Expression	[45]
DNAH5	OTC21RUS	Strong	Biomarker	[46]
HEY2	OTU4J3ZI	Strong	Altered Expression	[47]
HIRA	OTON40EJ	Strong	Biomarker	[48]
INVS	OT8KPESR	Strong	Biomarker	[49]
LRPAP1	OT6DVD2Q	Strong	Biomarker	[50]
MKKS	OTLF5T11	Strong	Genetic Variation	[51]
MKS1	OT83W5PB	Strong	Biomarker	[52]
PFKL	OTVHGAT7	Strong	Biomarker	[53]
PHC1	OT1JMX8U	Strong	Biomarker	[54]
REC8	OT6JAVXE	Strong	Genetic Variation	[18]
SUN2	OT2IQJUC	Strong	Biomarker	[50]
TBX20	OTMPU2XQ	Strong	Posttranslational Modification	[55]
TSPYL2	OTGGW2EF	Strong	Altered Expression	[50]
NKX2-5	OTS1SAWM	Definitive	Autosomal dominant	[56]
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⏷ Show the Full List of 53 DOT(s)

This Disease Is Related to 18 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
COMT	TTKWFB8	Limited	Biomarker	[3]
EPHB4	TTI4ZX2	Limited	Genetic Variation	[4]
FN1	TTPJ921	Limited	Biomarker	[5]
NPPB	TTY63XT	Limited	Altered Expression	[6]
OPRD1	TT27RFC	Limited	Biomarker	[7]
RPH3A	TT9L4J8	Limited	Genetic Variation	[8]
SH2B3	TT36N7Z	Limited	Genetic Variation	[8]
FLT4	TTDCBX5	Supportive	Autosomal dominant	[9]
GATA4	TT1VDN2	Supportive	Autosomal dominant	[10]
FOXC2	TTLBAP1	moderate	Biomarker	[11]
MBNL2	TTH9OLG	moderate	Altered Expression	[12]
FLT4	TTDCBX5	Strong	Genetic Variation	[9]
FOXC1	TTNT3YA	Strong	Biomarker	[11]
GJA5	TTFQKZ7	Strong	Genetic Variation	[13]
MAP4	TT0VFPN	Strong	Posttranslational Modification	[14]
NRP1	TTIPJCB	Strong	Genetic Variation	[15]
NTF3	TTZHKV9	Strong	Biomarker	[16]
WWP2	TT6TU05	Strong	Biomarker	[17]
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⏷ Show the Full List of 18 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC50A1	DTI9CQU	Strong	Genetic Variation	[18]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SULT1E1	DESTKG6	Limited	Biomarker	[19]
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References

1	Alprostadil FDA Label
2	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3	Association of tetralogy of Fallot with a distinct region of del22q11.2.Am J Med Genet. 2002 Feb 1;107(4):294-8. doi: 10.1002/ajmg.10166.
4	Family Based Whole Exome Sequencing Reveals the Multifaceted Role of Notch Signaling in Congenital Heart Disease.PLoS Genet. 2016 Oct 19;12(10):e1006335. doi: 10.1371/journal.pgen.1006335. eCollection 2016 Oct.
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6	Amino-terminal fragment of pro-brain natriuretic hormone identifies functional impairment and right ventricular overload in operated tetralogy of Fallot patients.Pediatr Cardiol. 2007 Sep-Oct;28(5):339-45. doi: 10.1007/s00246-007-0009-8. Epub 2007 Jun 29.
7	Effects of Prenatal PM(10) Exposure on Fetal Cardiovascular Malformations in Fuzhou, China: A Retrospective Case-Control Study.Environ Health Perspect. 2017 May 25;125(5):057001. doi: 10.1289/EHP289.
8	Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.Hum Mol Genet. 2013 Apr 1;22(7):1473-81. doi: 10.1093/hmg/dds552. Epub 2013 Jan 7.
9	Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot. Genet Med. 2019 Apr;21(4):1001-1007. doi: 10.1038/s41436-018-0260-9. Epub 2018 Sep 20.
10	GATA4 loss-of-function mutations underlie familial tetralogy of fallot. Hum Mutat. 2013 Dec;34(12):1662-71. doi: 10.1002/humu.22434. Epub 2013 Sep 17.
11	Functionally significant, rare transcription factor variants in tetralogy of Fallot.PLoS One. 2014 Aug 5;9(8):e95453. doi: 10.1371/journal.pone.0095453. eCollection 2014.
12	scaRNAs regulate splicing and vertebrate heart development.Biochim Biophys Acta. 2015 Aug;1852(8):1619-29. doi: 10.1016/j.bbadis.2015.04.016. Epub 2015 Apr 23.
13	A variant in the carboxyl-terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot.Eur J Hum Genet. 2013 Jan;21(1):69-75. doi: 10.1038/ejhg.2012.109. Epub 2012 Jun 20.
14	Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice.EBioMedicine. 2018 Nov;37:221-235. doi: 10.1016/j.ebiom.2018.10.017. Epub 2018 Oct 13.
15	Functional polymorphisms of the neuropilin 1 gene are associated with the risk of tetralogy of Fallot in a Chinese Han population.Gene. 2018 May 5;653:72-79. doi: 10.1016/j.gene.2018.02.027. Epub 2018 Feb 10.
16	LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development.Neuron. 2009 Sep 10;63(5):614-27. doi: 10.1016/j.neuron.2009.07.031.
17	WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling.Nat Commun. 2019 Aug 9;10(1):3616. doi: 10.1038/s41467-019-11551-9.
18	San Luis Valley recombinant chromosome 8 and tetralogy of Fallot: a review of chromosome 8 anomalies and congenital heart disease.Am J Med Genet. 1991 Sep 15;40(4):471-6. doi: 10.1002/ajmg.1320400420.
19	The evaluation of right ventricular systolic function in patients with repaired Tetralogy of Fallot by conventional echocardiographic methods and speckle tracking echocardiography: Compared with the gold standard cardiac mangenetic resonance.Echocardiography. 2019 Dec;36(12):2251-2258. doi: 10.1111/echo.14532. Epub 2019 Nov 22.
20	Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
21	4q25 microdeletion encompassing PITX2: A patient presenting with tetralogy of Fallot and dental anomalies without ocular features.Eur J Med Genet. 2018 Feb;61(2):72-78. doi: 10.1016/j.ejmg.2017.10.018. Epub 2017 Oct 31.
22	Whether Pulmonary Valve Replacement in Asymptomatic Patients With Moderate or Severe Regurgitation After Tetralogy of Fallot Repair Is Appropriate: A Case-Control Study.J Am Heart Assoc. 2019 Jan 8;8(1):e010689. doi: 10.1161/JAHA.118.010689.
23	Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot.Am J Med Genet A. 2015 Nov;167A(11):2702-6. doi: 10.1002/ajmg.a.37210. Epub 2015 Jul 2.
24	Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.J Mol Cell Cardiol. 2017 May;106:1-13. doi: 10.1016/j.yjmcc.2017.03.006. Epub 2017 Mar 27.
25	GATA5 loss-of-function mutations underlie tetralogy of fallot. Int J Med Sci. 2013;10(1):34-42. doi: 10.7150/ijms.5270. Epub 2012 Dec 10.
26	Mutational analysis of JAG1 gene in non-syndromic tetralogy of Fallot children. Clin Chim Acta. 2011 Nov 20;412(23-24):2232-6. doi: 10.1016/j.cca.2011.08.017. Epub 2011 Aug 27.
27	Oesophageal atresia with tracheoesophageal fistula and anal atresia in a patient with a de novo microduplication in 17q12.Eur J Med Genet. 2014 Jan;57(1):40-3. doi: 10.1016/j.ejmg.2013.10.007. Epub 2013 Nov 12.
28	Subarachnoid Hemorrhage Attributable to Bilateral Aplastic or Twiglike Middle Cerebral Artery.World Neurosurg. 2020 Feb;134:560-563. doi: 10.1016/j.wneu.2019.10.054. Epub 2019 Oct 16.
29	Prenatal diagnosis and molecular cytogenetic characterization of a de novo 4.858-Mb microdeletion in 15q14 associated with ACTC1 and MEIS2 haploinsufficiency and tetralogy of Fallot.Taiwan J Obstet Gynecol. 2016 Apr;55(2):270-4. doi: 10.1016/j.tjog.2016.02.013.
30	Remodeling of the hypertrophied human myocardium by cardiac bHLH transcription factors.J Cell Biochem. 1999 Sep 15;74(4):551-61. doi: 10.1002/(sici)1097-4644(19990915)74:4<551::aid-jcb5>3.3.co;2-0.
31	The Impact of the Right Ventricular Outflow Tract Patch on Right Ventricular Strain in Tetralogy of Fallot: A Comparison with Valvar Pulmonary Stenosis Utilizing Cardiac Magnetic Resonance.Pediatr Cardiol. 2017 Mar;38(3):617-623. doi: 10.1007/s00246-016-1558-5. Epub 2017 Jan 31.
32	Monitoring both procalcitonin and C-reactive protein in the early period after tetralogy of Fallot correction in children promotes rational antibiotic use.Adv Med Sci. 2018 Mar;63(1):112-118. doi: 10.1016/j.advms.2017.10.003. Epub 2017 Oct 27.
33	Genetic variation in VEGF does not contribute significantly to the risk of congenital cardiovascular malformation.PLoS One. 2009;4(3):e4978. doi: 10.1371/journal.pone.0004978. Epub 2009 Mar 24.
34	A Rare Rs139365823 Polymorphism in Pre-miR-138 Is Associated with Risk of Congenital Heart Disease in a Chinese Population.DNA Cell Biol. 2018 Feb;37(2):109-116. doi: 10.1089/dna.2017.4013. Epub 2018 Jan 3.
35	Mutational and functional analysis of the BVES gene coding region in Chinese patients with non-syndromic tetralogy of Fallot.Int J Mol Med. 2013 Apr;31(4):899-903. doi: 10.3892/ijmm.2013.1275. Epub 2013 Feb 7.
36	A novel HAND2 loss-of-function mutation responsible for tetralogy of Fallot.Int J Mol Med. 2016 Feb;37(2):445-51. doi: 10.3892/ijmm.2015.2436. Epub 2015 Dec 15.
37	miRNA-940 reduction contributes to human Tetralogy of Fallot development.J Cell Mol Med. 2014 Sep;18(9):1830-9. doi: 10.1111/jcmm.12309. Epub 2014 Jun 1.
38	Vancomycin heteroresistant community associated methicillin-resistant Staphylococcus aureus ST72-SCCmecIVa strain colonizing the nostrils of a five-year-old Spanish girl.Enferm Infecc Microbiol Clin. 2017 Mar;35(3):148-152. doi: 10.1016/j.eimc.2016.07.015. Epub 2016 Aug 31.
39	Prevalence and spectrum of Nkx2.6 mutations in patients with congenital heart disease.Eur J Med Genet. 2014 Oct;57(10):579-86. doi: 10.1016/j.ejmg.2014.08.005. Epub 2014 Sep 3.
40	Pbx/Meis deficiencies demonstrate multigenetic origins of congenital heart disease.Circ Res. 2008 Sep 26;103(7):702-9. doi: 10.1161/CIRCRESAHA.108.175489. Epub 2008 Aug 21.
41	Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease.Cardiovasc Pathol. 2013 Mar-Apr;22(2):141-5. doi: 10.1016/j.carpath.2012.07.001. Epub 2012 Sep 6.
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43	Clinical application of targeted next-generation sequencing in fetuses with congenital heart defect.Ultrasound Obstet Gynecol. 2018 Aug;52(2):205-211. doi: 10.1002/uog.19042. Epub 2018 Jun 25.
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45	DGCR8 expression is altered in children with congenital heart defects.Clin Chim Acta. 2019 Aug;495:25-28. doi: 10.1016/j.cca.2019.03.1619. Epub 2019 Mar 26.
46	Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia.J Clin Invest. 2007 Dec;117(12):3742-52. doi: 10.1172/JCI33284.
47	Duplication of HEY2 in cardiac and neurologic development.Am J Med Genet A. 2015 Sep;167A(9):2145-9. doi: 10.1002/ajmg.a.37086. Epub 2015 Apr 1.
48	HIRA Gene is Lower Expressed in the Myocardium of Patients with Tetralogy of Fallot.Chin Med J (Engl). 2016 Oct 20;129(20):2403-2408. doi: 10.4103/0366-6999.191745.
49	Situs variation and cardiovascular anomalies in the transgenic mouse insertional mutation, inv.Teratology. 1998 Jun;57(6):302-9. doi: 10.1002/(SICI)1096-9926(199806)57:6<302::AID-TERA3>3.0.CO;2-Y.
50	Isolation of differentially expressed genes in human heart tissues.Biochim Biophys Acta. 2002 Dec 12;1588(3):241-6. doi: 10.1016/s0925-4439(02)00171-0.
51	A female with complete lack of Mllerian fusion, postaxial polydactyly, and tetralogy of fallot: genetic heterogeneity of McKusick-Kaufman syndrome or a unique syndrome?.Am J Med Genet A. 2004 Aug 15;129A(1):69-72. doi: 10.1002/ajmg.a.30071.
52	Genome-wide identification of mouse congenital heart disease loci.Hum Mol Genet. 2010 Aug 15;19(16):3105-13. doi: 10.1093/hmg/ddq211. Epub 2010 May 28.
53	Down syndrome congenital heart disease: a narrowed region and a candidate gene.Genet Med. 2001 Mar-Apr;3(2):91-101. doi: 10.1097/00125817-200103000-00002.
54	Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells.J Exp Med. 2002 Mar 18;195(6):759-70. doi: 10.1084/jem.20011911.
55	DNA methylation status of TBX20 in patients with tetralogy of Fallot.BMC Med Genomics. 2019 May 28;12(1):75. doi: 10.1186/s12920-019-0534-3.
56	NKX2.5 mutations in patients with tetralogy of fallot. Circulation. 2001 Nov 20;104(21):2565-8. doi: 10.1161/hc4601.098427.