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==Pathophysiology==
==Pathophysiology==
===Tetrology of Fallot===
===Tetrology of Fallot===
The obstruction of right ventricular outflow in Tetralogy of Fallot causes blood to shunt or flow from the right to left side of heart through the [[ventricular septal defect]]. This causes right ventricular hypertrophy and eventual right sided heart failure.  There is flow of deoxygenated venous blood from the right side of the heart to the systemic circulation resulting in [[cyanosis]].
* It is understood that tetralogy of fallot is the result of improper positioning of the outlet [[septum]].<ref name="pmid19094375">{{cite journal| author=Anderson RH, Jacobs ML| title=The anatomy of tetralogy of Fallot with pulmonary stenosis. | journal=Cardiol Young | year= 2008 | volume= 18 Suppl 3 | issue=  | pages= 12-21 | pmid=19094375 | doi=10.1017/S1047951108003259 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19094375  }} </ref><ref name="pmid17420363">{{cite journal| author=Bashore TM| title=Adult congenital heart disease: right ventricular outflow tract lesions. | journal=Circulation | year= 2007 | volume= 115 | issue= 14 | pages= 1933-47 | pmid=17420363 | doi=10.1161/CIRCULATIONAHA.105.592345 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17420363  }} </ref><ref name="pmid19144126">{{cite journal| author=Bailliard F, Anderson RH| title=Tetralogy of Fallot. | journal=Orphanet J Rare Dis | year= 2009 | volume= 4 | issue=  | pages= 2 | pmid=19144126 | doi=10.1186/1750-1172-4-2 | pmc=PMC2651859 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19144126  }} </ref>
* In the normal [[heart]], the outlet septum is an indistinguishable component of the crista supraventricularis that communicates with the [[Septomarginal trabecula|septomarginal trabeculae]] to divide the [[Right ventricle|right]] and [[Left ventricle|left]] [[Ventricle|ventricular cavities]].
* In Tetralogy of Fallot, proper [[Ventricle (heart)|ventricular]] septation is perturbed by anterocephalad displacement of the outlet [[Septum (disambiguation)|septum]] relative to the [[septomarginal trabecula]].
* The direct consequence of this misalignment is an [[Overriding aorta|overriding aortic orifice]] and a [[ventricular septal defect]], resulting in an intracardiac [[Right-to-left shunt|right to left shunt]] of blood.
* In addition, anterocephalad displacement of the outlet septum indirectly predisposes the [[pulmonary trunk]] to [[Pulmonary stenosis|stenosis]] in the setting of septoparietal trabecular [[hypertrophy]].
* Together, the displacement of the outlet [[septum]] coupled with the [[Hypertrophy (medical)|hypertrophic]] arrangement of the septoparietal trabeculae account for the three [[Anatomy|anatomical]] cardinal [[Defect|defects]] in Tetralogy of Fallot - [[Aorta|aortic]] dextroposition, [[Ventricular septal defect|interventricular communication]] ([[VSD]]), and [[pulmonary stenosis]].
* The fourth [[defect]] - [[right ventricular hypertrophy]] - is a [[hemodynamic]] consequence of these three [[Morphology|morphologic]] changes, as the [[right ventricle]] physiologically adapts to the increased [[resistance]] of a [[Pulmonary stenosis|stenotic pulmonary trunk]].
*


===Total Anomalous Pulmonary Venous Connection===
===Total Anomalous Pulmonary Venous Connection===
In this condition,the right side of heart is receiving blood both from pulmonary and systemic circulation. There is a mixing of oxygenated pulmonary venous blood with deoxygenated blood from systemic circulation. The mixing of blood could occur at three levels i.e. supracardiac, infracardiac and cardiac. In the former two the mixing occurs outside the heart and in latter inside the heart (right atrium)


===Hypoplastic Left Heart Syndrome===
* In this condition,the right side of heart is receiving blood both from pulmonary and systemic circulation.<ref name="pmid13378917">{{cite journal |vauthors=NEILL CA |title=Development of the pulmonary veins; with reference to the embryology of anomalies of pulmonary venous return |journal=Pediatrics |volume=18 |issue=6 |pages=880–7 |date=December 1956 |pmid=13378917 |doi= |url=}}</ref><ref name="pmid13386206">{{cite journal |vauthors=CRAIG JM, DARLING RC, ROTHNEY WB |title=Total pulmonary venous drainage into the right side of the heart; report of 17 autopsied cases not associated with other major cardiovascular anomalies |journal=Lab. Invest. |volume=6 |issue=1 |pages=44–64 |date=1957 |pmid=13386206 |doi= |url=}}</ref>
* There is a mixing of oxygenated pulmonary venous blood with deoxygenated blood from systemic circulation.
* The mixing of blood could occur at three levels i.e. supracardiac, infracardiac and cardiac.
* In the former two the mixing occurs outside the heart and in latter inside the heart (right atrium)


In patients with hypoplastic left heart syndrome, the left side of the heart is unable to send enough blood to the body. As a result, the right side of the heart must maintain the circulation for both the lungs and the body. The right ventricle can support the circulation to both the lungs and the body for a while, but this extra workload eventually causes the right side of the heart to fail.
===Transpostion of Great Arteries===


===Transpostion of Great Arteries===
*In the TGA the [[aorta]] arises from the morphologic [[right ventricle]] via a subaortic infundibulum and the [[pulmonary artery]] arises from the morphologic [[left ventricle]], without a subpulmonary infundibulum.<ref name="pmid17159076">{{cite journal |vauthors=Warnes CA |title=Transposition of the great arteries |journal=Circulation |volume=114 |issue=24 |pages=2699–709 |date=December 2006 |pmid=17159076 |doi=10.1161/CIRCULATIONAHA.105.592352 |url=}}</ref><ref name="Levin1977">{{cite journal|last1=Levin|first1=Daniel L.|title=d-Transposition of the Great Vessels in the Neonate|journal=Archives of Internal Medicine|volume=137|issue=10|year=1977|pages=1421|issn=0003-9926|doi=10.1001/archinte.1977.03630220061015}}</ref><ref name="Rashkind1966">{{cite journal|last1=Rashkind|first1=William J.|title=Creation of an Atrial Septal Defect Without Thoracotomy|journal=JAMA|volume=196|issue=11|year=1966|pages=991|issn=0098-7484|doi=10.1001/jama.1966.03100240125026}}</ref><ref name="pmid10569681">{{cite journal |vauthors=Hornung TS, Bernard EJ, Celermajer DS, Jaeggi E, Howman-Giles RB, Chard RB, Hawker RE |title=Right ventricular dysfunction in congenitally corrected transposition of the great arteries |journal=Am. J. Cardiol. |volume=84 |issue=9 |pages=1116–9, A10 |date=November 1999 |pmid=10569681 |doi=10.1016/s0002-9149(99)00516-0 |url=}}</ref>
The pulmonary and systemic circulations function in parallel, rather than in series. Oxygenated pulmonary venous blood returns to the left atrium and left ventricle but is recirculated to the pulmonary vascular bed and deoxygenated systemic venous blood returns into right atrium and ventricle which is subsequently pumped back into systemic circulation.
*These ventriculoarterial connection is known as ventriculoarterial discordance.
* As a consequence, there is a a fibrous continuity between the mitral and [[pulmonary valve]], but no continuity between the [[tricuspid]] and [[aortic valve]].
*The abnormal origin of the great arteries results in an altered spiral relationship.
*Therefore, the aorta and pulmonary artery run parallel to each other
*In normal heart thus the circulation is in series.
*However, in transposition of the great vessels circulation is in parallel


===Truncus Arteriosus===
===Truncus Arteriosus===
In truncus arteriosus, the pulmonary arteries are connected to the aorta. A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure. These patients have a very high incidence of pulmonary hypertension and vascular disease.
 
* In truncus arteriosus, the pulmonary arteries are connected to the aorta.
* A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure.
* These patients have a very high incidence of pulmonary hypertension and vascular disease.


===Tricuspid Atresia===
===Tricuspid Atresia===
In tricuspid atresia, there is no continuity between the right atrium and right ventricle. Blood from superior vena cava and inferior vena cava is forced across intra atrial connection into the left heart. As a consequence, oxygen saturation in the left atrial blood is diminished.
 
* In tricuspid atresia, there is no continuity between the right atrium and right ventricle. Blood from superior vena cava and inferior vena cava is forced across intra atrial connection into the left heart.
* As a consequence, oxygen saturation in the left atrial blood is diminished.
 
===Hypoplastic Left Heart Syndrome===
 
* In patients with hypoplastic left heart syndrome, the left side of the heart is unable to send enough blood to the body.
* As a result, the right side of the heart must maintain the circulation for both the lungs and the body.
* The right ventricle can support the circulation to both the lungs and the body for a while, but this extra workload eventually causes the right side of the heart to fail.
 
==Genetics==
*[[Genes]] involved in the [[pathogenesis]] of tetralogy of fallot include:<ref name="pmid17008524">{{cite journal| author=Olson EN| title=Gene regulatory networks in the evolution and development of the heart. | journal=Science | year= 2006 | volume= 313 | issue= 5795 | pages= 1922-7 | pmid=17008524 | doi=10.1126/science.1132292 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17008524  }} </ref><ref name="pmid24000169">{{cite journal| author=Yang YQ, Gharibeh L, Li RG, Xin YF, Wang J, Liu ZM et al.| title=GATA4 loss-of-function mutations underlie familial tetralogy of fallot. | journal=Hum Mutat | year= 2013 | volume= 34 | issue= 12 | pages= 1662-71 | pmid=24000169 | doi=10.1002/humu.22434 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24000169  }} </ref><ref name="pmid18288184">{{cite journal| author=Bruneau BG| title=The developmental genetics of congenital heart disease. | journal=Nature | year= 2008 | volume= 451 | issue= 7181 | pages= 943-8 | pmid=18288184 | doi=10.1038/nature06801 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18288184  }} </ref><ref name="pmid24526674">{{cite journal| author=Bruneau BG, Srivastava D| title=Congenital heart disease: entering a new era of human genetics. | journal=Circ Res | year= 2014 | volume= 114 | issue= 4 | pages= 598-9 | pmid=24526674 | doi=10.1161/CIRCRESAHA.113.303060 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24526674  }} </ref><ref name="pmid11431700">{{cite journal| author=Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R et al.| title=Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. | journal=Nat Genet | year= 2001 | volume= 28 | issue= 3 | pages= 276-80 | pmid=11431700 | doi=10.1038/90123 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11431700  }} </ref><ref name="pmid12845333">{{cite journal| author=Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA et al.| title=GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. | journal=Nature | year= 2003 | volume= 424 | issue= 6947 | pages= 443-7 | pmid=12845333 | doi=10.1038/nature01827 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12845333  }} </ref><ref name="pmid24182332">{{cite journal| author=Sheng W, Qian Y, Wang H, Ma X, Zhang P, Diao L et al.| title=DNA methylation status of NKX2-5, GATA4 and HAND1 in patients with tetralogy of fallot. | journal=BMC Med Genomics | year= 2013 | volume= 6 | issue=  | pages= 46 | pmid=24182332 | doi=10.1186/1755-8794-6-46 | pmc=PMC3819647 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24182332  }} </ref>
** The [[cellular]] processes that underlie cardiogenesis are extensively regulated in the developing [[heart]].
** Proper [[Heart|cardiac]] development requires the complex orchestration of [[cardiac]] [[Transcription factor|transcription factors]] and [[Signaling pathway|signaling pathways]] in a spatiotemporal specific manner.
** Previous [[Genetics|genetic]] studies demonstrated that [[mutations]] in numerous [[genes]] encoding [[Heart|cardiac]] [[transcription factors]] and [[cell]] [[Signaling protein|signaling proteins]] have a role in the [[development]] of Tetralogy of Fallot.
** Specifically, [[Heterozygous|heterozygous mutations]] in [[NKX2-5]], [[HAND1]], [[TBX5 (gene)|TBX5]], and [[GATA4]] have been reported in familial forms of [[disease]].
** Many of these single [[Gene mutation|gene mutations]] result in [[haploinsufficiency]] and suggest a dose dependent relationship between [[genetic]] expression and [[disease]].
** While the mechanistic basis of this relationship is currently poorly understood, it is hypothesized that disruption of the direct [[protein]]-[[protein]] interactions that allow these [[transcription factors]] to work synergistically impedes the activation of downstream targets and [[signaling pathway]]<nowiki/>s central to [[cardiac]] morphogenesis.
** In addition, recent whole-exome sequencing investigations have introduced a novel role for [[Epigenetics|epigenetic]] dysregulation in the [[pathogenesis]] of Tetralogy of Fallot.
** Aberrant [[epigenetic]] modifications are thought to provide an alternative mechanism to perturb normal spatiotemporal expression of these essential [[developmental]] [[genes]].
 
* [[Genetic]] [[mutations]] associated with total anomalous pulmonary venous connection include:<ref name="PhelanMcDermid2011">{{cite journal|last1=Phelan|first1=K.|last2=McDermid|first2=H.E.|title=The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)|journal=Molecular Syndromology|year=2011|issn=1661-8777|doi=10.1159/000334260}}</ref><ref name="BleylSaijoh2010">{{cite journal|last1=Bleyl|first1=Steven B.|last2=Saijoh|first2=Yukio|last3=Bax|first3=Noortje A.M.|last4=Gittenberger-de Groot|first4=Adriana C.|last5=Wisse|first5=Lambertus J.|last6=Chapman|first6=Susan C.|last7=Hunter|first7=Jennifer|last8=Shiratori|first8=Hidetaka|last9=Hamada|first9=Hiroshi|last10=Yamada|first10=Shigehito|last11=Shiota|first11=Kohei|last12=Klewer|first12=Scott E.|last13=Leppert|first13=Mark F.|last14=Schoenwolf|first14=Gary C.|title=Dysregulation of the PDGFRA gene causes inflow tract anomalies including TAPVR: integrating evidence from human genetics and model organisms|journal=Human Molecular Genetics|volume=19|issue=7|year=2010|pages=1286–1301|issn=0964-6906|doi=10.1093/hmg/ddq005}}</ref>
 
 
 
 
 
==Associated Conditions==
* Conditions associated with tetralogy of fallot include:<ref name="pmid7349946">{{cite journal |vauthors=Dabizzi RP, Caprioli G, Aiazzi L, Castelli C, Baldrighi G, Parenzan L, Baldrighi V |title=Distribution and anomalies of coronary arteries in tetralogy of fallot |journal=Circulation |volume=61 |issue=1 |pages=95–102 |date=January 1980 |pmid=7349946 |doi=10.1161/01.cir.61.1.95 |url=}}</ref><ref name="Satyanarayana RaoAnderson1971">{{cite journal|last1=Satyanarayana Rao|first1=B.N.|last2=Anderson|first2=Ray C.|last3=Edwards|first3=Jesse E.|title=Anatomic variations in the tetralogy of Fallot|journal=American Heart Journal|volume=81|issue=3|year=1971|pages=361–371|issn=00028703|doi=10.1016/0002-8703(71)90106-2}}</ref><ref name="MusterPaul1973">{{cite journal|last1=Muster|first1=Alexander J.|last2=Paul|first2=Milton H.|last3=Nikaidoh|first3=Hisashi|title=Tetralogy of Fallot Associated with Total Anomalous Pulmonary Venous Drainage|journal=Chest|volume=64|issue=3|year=1973|pages=323–326|issn=00123692|doi=10.1378/chest.64.3.323}}</ref><ref name="SaifiMatsumoto2012">{{cite journal|last1=Saifi|first1=Comron|last2=Matsumoto|first2=Hiroko|last3=Vitale|first3=Michael G.|last4=Roye|first4=David P.|last5=Hyman|first5=Joshua E.|title=The incidence of congenital scoliosis in infants with tetralogy of Fallot based on chest radiographs|journal=Journal of Pediatric Orthopaedics B|volume=21|issue=4|year=2012|pages=313–316|issn=1060-152X|doi=10.1097/BPB.0b013e3283536872}}</ref>
**Left [[superior vena cava]]
**[[Anomaly|Anomalies]] of the [[mitral valve]]
**[[Anomaly|Anomalies]] of the [[tricuspid valve]]
**[[pulmonic stenosis|Stenosis of the left pulmonary artery]], in 40% of [[Patient|patients]]
** A bicuspid [[Pulmonic regurgitation|pulmonary valve]], in 40% of [[patients]]
** Right sided [[aortic arch]], in 25% of [[patients]]
**[[Coronary artery anomalies]], in 10% of [[patients]]
** An [[atrial septal defect]], in which case the [[DRESS syndrome|syndrome]] is sometimes called a [[pentalogy of Fallot]].
** An [[atrioventricular septal defect]]
** Partially or totally [[anomalous pulmonary venous return]]
** Forked ribs and [[scoliosis]]
**Associated [[abnormalities]] include [[cleft lip]], [[cleft palate]], [[hypospadias]], [[Skeleton|skeletal]] and [[craniofacial]] [[abnormalities]].
 
* Conditions associated with total anomalous pulmonary venous connection
**[[Patent foramen ovale]]
**[[Atrial septal defect]]
**[[Patent ductus arteriosus]]
**[[Pulmonary hypertension]]
* Conditions associated with TGA include:
**[[Ventricular septal defect]]
**[[Pulmonary stenosis]]
**Left atrioventricular valve regurgitation (tricuspid or systemic)
**[[Complete heart block]]
* Conditions associated with truncus arteriosus include:
** DiGeorge syndrome
**
 
 
 
 
==Gross Pathology==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


==References==
==References==

Latest revision as of 16:17, 14 April 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Keri Shafer, M.D. [2], Atif Mohammad, M.D.; Kalsang Dolma, M.B.B.S.[3]

Overview

Pathophysiology

Tetrology of Fallot

Total Anomalous Pulmonary Venous Connection

  • In this condition,the right side of heart is receiving blood both from pulmonary and systemic circulation.[4][5]
  • There is a mixing of oxygenated pulmonary venous blood with deoxygenated blood from systemic circulation.
  • The mixing of blood could occur at three levels i.e. supracardiac, infracardiac and cardiac.
  • In the former two the mixing occurs outside the heart and in latter inside the heart (right atrium)

Transpostion of Great Arteries

  • In the TGA the aorta arises from the morphologic right ventricle via a subaortic infundibulum and the pulmonary artery arises from the morphologic left ventricle, without a subpulmonary infundibulum.[6][7][8][9]
  • These ventriculoarterial connection is known as ventriculoarterial discordance.
  • As a consequence, there is a a fibrous continuity between the mitral and pulmonary valve, but no continuity between the tricuspid and aortic valve.
  • The abnormal origin of the great arteries results in an altered spiral relationship.
  • Therefore, the aorta and pulmonary artery run parallel to each other
  • In normal heart thus the circulation is in series.
  • However, in transposition of the great vessels circulation is in parallel

Truncus Arteriosus

  • In truncus arteriosus, the pulmonary arteries are connected to the aorta.
  • A decrease in PVR at birth causes a left to right shunt with evidence of congestive heart failure.
  • These patients have a very high incidence of pulmonary hypertension and vascular disease.

Tricuspid Atresia

  • In tricuspid atresia, there is no continuity between the right atrium and right ventricle. Blood from superior vena cava and inferior vena cava is forced across intra atrial connection into the left heart.
  • As a consequence, oxygen saturation in the left atrial blood is diminished.

Hypoplastic Left Heart Syndrome

  • In patients with hypoplastic left heart syndrome, the left side of the heart is unable to send enough blood to the body.
  • As a result, the right side of the heart must maintain the circulation for both the lungs and the body.
  • The right ventricle can support the circulation to both the lungs and the body for a while, but this extra workload eventually causes the right side of the heart to fail.

Genetics



Associated Conditions



Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References

  1. Anderson RH, Jacobs ML (2008). "The anatomy of tetralogy of Fallot with pulmonary stenosis". Cardiol Young. 18 Suppl 3: 12–21. doi:10.1017/S1047951108003259. PMID 19094375.
  2. Bashore TM (2007). "Adult congenital heart disease: right ventricular outflow tract lesions". Circulation. 115 (14): 1933–47. doi:10.1161/CIRCULATIONAHA.105.592345. PMID 17420363.
  3. Bailliard F, Anderson RH (2009). "Tetralogy of Fallot". Orphanet J Rare Dis. 4: 2. doi:10.1186/1750-1172-4-2. PMC 2651859. PMID 19144126.
  4. NEILL CA (December 1956). "Development of the pulmonary veins; with reference to the embryology of anomalies of pulmonary venous return". Pediatrics. 18 (6): 880–7. PMID 13378917.
  5. CRAIG JM, DARLING RC, ROTHNEY WB (1957). "Total pulmonary venous drainage into the right side of the heart; report of 17 autopsied cases not associated with other major cardiovascular anomalies". Lab. Invest. 6 (1): 44–64. PMID 13386206.
  6. Warnes CA (December 2006). "Transposition of the great arteries". Circulation. 114 (24): 2699–709. doi:10.1161/CIRCULATIONAHA.105.592352. PMID 17159076.
  7. Levin, Daniel L. (1977). "d-Transposition of the Great Vessels in the Neonate". Archives of Internal Medicine. 137 (10): 1421. doi:10.1001/archinte.1977.03630220061015. ISSN 0003-9926.
  8. Rashkind, William J. (1966). "Creation of an Atrial Septal Defect Without Thoracotomy". JAMA. 196 (11): 991. doi:10.1001/jama.1966.03100240125026. ISSN 0098-7484.
  9. Hornung TS, Bernard EJ, Celermajer DS, Jaeggi E, Howman-Giles RB, Chard RB, Hawker RE (November 1999). "Right ventricular dysfunction in congenitally corrected transposition of the great arteries". Am. J. Cardiol. 84 (9): 1116–9, A10. doi:10.1016/s0002-9149(99)00516-0. PMID 10569681.
  10. Olson EN (2006). "Gene regulatory networks in the evolution and development of the heart". Science. 313 (5795): 1922–7. doi:10.1126/science.1132292. PMID 17008524.
  11. Yang YQ, Gharibeh L, Li RG, Xin YF, Wang J, Liu ZM; et al. (2013). "GATA4 loss-of-function mutations underlie familial tetralogy of fallot". Hum Mutat. 34 (12): 1662–71. doi:10.1002/humu.22434. PMID 24000169.
  12. Bruneau BG (2008). "The developmental genetics of congenital heart disease". Nature. 451 (7181): 943–8. doi:10.1038/nature06801. PMID 18288184.
  13. Bruneau BG, Srivastava D (2014). "Congenital heart disease: entering a new era of human genetics". Circ Res. 114 (4): 598–9. doi:10.1161/CIRCRESAHA.113.303060. PMID 24526674.
  14. Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R; et al. (2001). "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation". Nat Genet. 28 (3): 276–80. doi:10.1038/90123. PMID 11431700.
  15. Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA; et al. (2003). "GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5". Nature. 424 (6947): 443–7. doi:10.1038/nature01827. PMID 12845333.
  16. Sheng W, Qian Y, Wang H, Ma X, Zhang P, Diao L; et al. (2013). "DNA methylation status of NKX2-5, GATA4 and HAND1 in patients with tetralogy of fallot". BMC Med Genomics. 6: 46. doi:10.1186/1755-8794-6-46. PMC 3819647. PMID 24182332.
  17. Phelan, K.; McDermid, H.E. (2011). "The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)". Molecular Syndromology. doi:10.1159/000334260. ISSN 1661-8777.
  18. Bleyl, Steven B.; Saijoh, Yukio; Bax, Noortje A.M.; Gittenberger-de Groot, Adriana C.; Wisse, Lambertus J.; Chapman, Susan C.; Hunter, Jennifer; Shiratori, Hidetaka; Hamada, Hiroshi; Yamada, Shigehito; Shiota, Kohei; Klewer, Scott E.; Leppert, Mark F.; Schoenwolf, Gary C. (2010). "Dysregulation of the PDGFRA gene causes inflow tract anomalies including TAPVR: integrating evidence from human genetics and model organisms". Human Molecular Genetics. 19 (7): 1286–1301. doi:10.1093/hmg/ddq005. ISSN 0964-6906.
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