1932

Abstract

Congenital heart disease is the most frequent birth defect and the leading cause of death for the fetus and in the first year of life. The wide phenotypic diversity of congenital heart defects requires expert diagnosis and sophisticated repair surgery. Although these defects have been described since the seventeenth century, it was only in 2005 that a consensus international nomenclature was adopted, followed by an international classification in 2017 to help provide better management of patients. Advances in genetic engineering, imaging, and omics analyses have uncovered mechanisms of heart formation and malformation in animal models, but approximately 80% of congenital heart defects have an unknown genetic origin. Here, we summarize current knowledge of congenital structural heart defects, intertwining clinical and fundamental research perspectives, with the aim to foster interdisciplinary collaborations at the cutting edge of each field. We also discuss remaining challenges in better understanding congenital heart defects and providing benefits to patients.

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2021-08-31
2024-06-14
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Literature Cited

  1. 1. 
    Abbott M. 1936. Atlas of Congenital Cardiac Disease. Can. Med. Assoc. J. 34:194–95
    [Google Scholar]
  2. 2. 
    Agnoleti G, Annecchino F, Preda L, Borghi A. 1999. Persistence of the left superior caval vein: Can it potentiate obstructive lesions of the left ventricle?. Cardiol. Young 9:285–90
    [Google Scholar]
  3. 3. 
    Anderson RH. 2017. Has the congenitally malformed heart changed its face? Journey from understanding morphology to surgical cure in congenital heart disease. Circ. Res. 120:901–3
    [Google Scholar]
  4. 4. 
    Anderson RH, Becker AE, Freedom RM, Macartney FJ, Quero-Jimenez M et al. 1984. Sequential segmental analysis of congenital heart disease. Pediatr. Cardiol. 5:281–87
    [Google Scholar]
  5. 5. 
    Anderson RH, Becker AE, Wilcox BR, Macartney FJ, Wilkinson JL. 1983. Surgical anatomy of double-outlet right ventricle—a reappraisal. Am. J. Cardiol. 52:555–59
    [Google Scholar]
  6. 6. 
    Anderson RH, Spicer DE, Brown NA, Mohun TJ. 2014. The development of septation in the four-chambered heart. Anat. Rec. 297:1414–29
    [Google Scholar]
  7. 7. 
    Anderson RH, Spicer DE, Mohun TJ, Hikspoors JPJM, Lamers WH. 2019. Remodeling of the embryonic interventricular communication in regard to the description and classification of ventricular septal defects. Anat. Rec. 302:19–31
    [Google Scholar]
  8. 8. 
    Arrechedera H, Alvarez M, Strauss M, Ayesta C. 1987. Origin of mesenchymal tissue in the septum primum: a structural and ultrastructural study. J. Mol. Cell. Cardiol. 19:641–51
    [Google Scholar]
  9. 9. 
    Bajolle F, Zaffran S, Kelly RG, Hadchouel J, Bonnet D et al. 2006. Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ. Res. 98:421–28
    [Google Scholar]
  10. 10. 
    Bajolle F, Zaffran S, Losay J, Ou P, Buckingham M, Bonnet D. 2009. Conotruncal defects associated with anomalous pulmonary venous connections. Arch. Cardiovasc. Dis. 102:105–10
    [Google Scholar]
  11. 11. 
    Bartelings MM, Gittenberger-de Groot AC. 1989. The outflow tract of the heart—embryologic and morphologic correlations. Int. J. Cardiol. 22:289–300
    [Google Scholar]
  12. 12. 
    Béland MJ, Franklin RC, Aiello VD, Houyel L, Weinberg PM, Anderson RH 2018. Nomenclature and classification of cardiac defects. Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care EM da Cruz, D Ivy, V Hraska, J Jaggers 1–23 London: Springer
    [Google Scholar]
  13. 13. 
    Ben-Shachar G, Arcilla RA, Lucas RV, Manasek FJ. 1985. Ventricular trabeculations in the chick embryo heart and their contribution to ventricular and muscular septal development. Circ. Res. 57:759–66
    [Google Scholar]
  14. 14. 
    Bernheim S, Meilhac SM. 2020. Mesoderm patterning by a dynamic gradient of retinoic acid signalling. Philos. Trans. R. Soc. Lond. B 375:20190556
    [Google Scholar]
  15. 15. 
    Blom NA, Ottenkamp J, Wenink AGC, Gittenberger-de Groot AC. 2003. Deficiency of the vestibular spine in atrioventricular septal defects in human fetuses with down syndrome. Am. J. Cardiol. 91:180–84
    [Google Scholar]
  16. 16. 
    Botto LD, Lin AE, Riehle-Colarusso T, Malik S, Correa A 2007. Seeking causes: classifying and evaluating congenital heart defects in etiologic studies. Birth Defects Res. A 79:714–27
    [Google Scholar]
  17. 17. 
    Briggs LE, Kakarla J, Wessels A. 2012. The pathogenesis of atrial and atrioventricular septal defects with special emphasis on the role of the dorsal mesenchymal protrusion. Differentiation 84:117–30
    [Google Scholar]
  18. 18. 
    Brown CB, Boyer AS, Runyan RB, Barnett JV. 1999. Requirement of type III TGF-β receptor for endocardial cell transformation in the heart. Science 283:2080–82
    [Google Scholar]
  19. 19. 
    Bruneau BG, Logan M, Davis N, Levi T, Tabin CJ et al. 1999. Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev. Biol. 211:100–8
    [Google Scholar]
  20. 20. 
    Burnicka-Turek O, Steimle JD, Huang W, Felker L, Kamp A et al. 2016. Cilia gene mutations cause atrioventricular septal defects by multiple mechanisms. Hum. Mol. Genet. 25:3011–28
    [Google Scholar]
  21. 21. 
    Celermajer DS, Bull C, Till JA, Cullen S, Vassillikos VP et al. 1994. Ebstein's anomaly: presentation and outcome from fetus to adult. J. Am. Coll. Cardiol. 23:170–76
    [Google Scholar]
  22. 22. 
    Chen B, Bronson RT, Klaman LD, Hampton TG, Wang JF et al. 2000. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat. Genet. 24:296–99
    [Google Scholar]
  23. 23. 
    Chun H, Yue Y, Wang Y, Dawa Z, Zhen P et al. 2019. High prevalence of congenital heart disease at high altitudes in Tibet. Eur. J. Prev. Cardiol. 26:756–59
    [Google Scholar]
  24. 24. 
    Conway SJ, Henderson DJ, Copp AJ. 1997. Pax3 is required for cardiac neural crest migration in the mouse: evidence from the splotch (Sp2H) mutant. Development 124:505–14
    [Google Scholar]
  25. 25. 
    Courchaine K, Rykiel G, Rugonyi S. 2018. Influence of blood flow on cardiac development. Prog. Biophys. Mol. Biol. 137:95–110
    [Google Scholar]
  26. 26. 
    Darrigrand J-F, Valente M, Comai G, Martinez P, Petit M et al. 2020. Dullard-mediated Smad1/5/8 inhibition controls mouse cardiac neural crest cells condensation and outflow tract septation. eLife 9:e50325
    [Google Scholar]
  27. 27. 
    De Bono C, Thellier C, Bertrand N, Sturny R, Jullian E et al. 2018. T-box genes and retinoic acid signaling regulate the segregation of arterial and venous pole progenitor cells in the murine second heart field. Hum. Mol. Genet. 27:3747–60
    [Google Scholar]
  28. 28. 
    de la Cruz MV, Anselmi G, Cisneros F, Reinhold M, Portillo B, Espino-Vela J. 1959. An embryologic explanation for the corrected transposition of the great vessels: additional description of the main anatomic features of this malformation and its varieties. Am. Heart J. 57:104–17
    [Google Scholar]
  29. 29. 
    de la Cruz MV, Castillo MM, Villavicencio L, Valencia A, Moreno-Rodriguez RA. 1997. Primitive interventricular septum, its primordium, and its contribution in the definitive interventricular septum: in vivo labelling study in the chick embryo heart. Anat. Rec. 247:512–20
    [Google Scholar]
  30. 30. 
    de Lange FJ, Moorman AFM, Anderson RH, Männer J, Soufan AT et al. 2004. Lineage and morphogenetic analysis of the cardiac valves. Circ. Res. 95:645–54
    [Google Scholar]
  31. 31. 
    de Soysa TY, Ranade SS, Okawa S, Ravichandran S, Huang Y et al. 2019. Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects. Nature 572:120–24
    [Google Scholar]
  32. 32. 
    Desgrange A, Le Garrec J-F, Bernheim S, Bønnelykke TH, Meilhac SM 2020. Transient nodal signaling in left precursors coordinates opposed asymmetries shaping the heart loop. Dev. Cell 55:413–31.e6
    [Google Scholar]
  33. 33. 
    Desgrange A, Lokmer J, Marchiol C, Houyel L, Meilhac SM. 2019. Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages. Dis. Model. Mech. 12:dmm038356
    [Google Scholar]
  34. 34. 
    Domínguez JN, Meilhac SM, Bland YS, Buckingham ME, Brown NA. 2012. Asymmetric fate of the posterior part of the second heart field results in unexpected left/right contributions to both poles of the heart. Circ. Res. 111:1323–35
    [Google Scholar]
  35. 35. 
    Eley L, Alqahtani AM, MacGrogan D, Richardson RV, Murphy L et al. 2018. A novel source of arterial valve cells linked to bicuspid aortic valve without raphe in mice. eLife 7:e34110
    [Google Scholar]
  36. 36. 
    Ellesøe SG, Workman CT, Bouvagnet P, Loffredo CA, McBride KL et al. 2018. Familial co-occurrence of congenital heart defects follows distinct patterns. Eur. Heart J. 39:1015–22
    [Google Scholar]
  37. 37. 
    Franco D, Meilhac SM, Christoffels VM, Kispert A, Buckingham M, Kelly RG. 2006. Left and right ventricular contributions to the formation of the interventricular septum in the mouse heart. Dev. Biol. 294:366–75
    [Google Scholar]
  38. 38. 
    Franklin RCG, Béland MJ, Colan SD, Walters HL, Aiello VD et al. 2017. Nomenclature for congenital and paediatric cardiac disease: the International Paediatric and Congenital Cardiac Code (IPCCC) and the eleventh iteration of the International Classification of Diseases (ICD-11). Cardiol. Young 27:1872–938
    [Google Scholar]
  39. 39. 
    Furtado MB, Biben C, Shiratori H, Hamada H, Harvey RP. 2011. Characterization of Pitx2c expression in the mouse heart using a reporter transgene. Dev. Dyn. 240:195–203
    [Google Scholar]
  40. 40. 
    Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R et al. 2005. Mutations in NOTCH1 cause aortic valve disease. Nature 437:270–74
    [Google Scholar]
  41. 41. 
    Gaussin V, Van de Putte T, Mishina Y, Hanks MC, Zwijsen A et al. 2002. Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. PNAS 99:2878–83
    [Google Scholar]
  42. 42. 
    Goddeeris MM, Schwartz R, Klingensmith J, Meyers EN. 2007. Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development. Development 134:1593–604
    [Google Scholar]
  43. 43. 
    Goldmuntz E, Bamford R, Karkera JD, dela Cruz J, Roessler E, Muenke M. 2002. CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle. Am. J. Hum. Genet. 70:776–80
    [Google Scholar]
  44. 44. 
    Guimier A, Gabriel GC, Bajolle F, Tsang M, Liu H et al. 2015. MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates. Nat. Genet. 47:1260–63
    [Google Scholar]
  45. 45. 
    Harh JY, Paul MH. 1975. Experimental cardiac morphogenesis. I. Development of the ventricular septum in the chick. J. Embryol. Exp. Morphol. 33:13–28
    [Google Scholar]
  46. 46. 
    Harrelson Z, Kelly RG, Goldin SN, Gibson-Brown JJ, Bollag RJ et al. 2004. Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development. Development 131:5041–52
    [Google Scholar]
  47. 47. 
    Hiermeier F, Männer J. 2017. Kinking and torsion can significantly improve the efficiency of valveless pumping in periodically compressed tubular conduits. Implications for understanding of the form-function relationship of embryonic heart tubes. J. Cardiovasc. Dev. Dis. 4:19
    [Google Scholar]
  48. 48. 
    Hinton RB, Lincoln J, Deutsch GH, Osinska H, Manning PB et al. 2006. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ. Res. 98:1431–38
    [Google Scholar]
  49. 49. 
    Hinton RB, Yutzey KE. 2011. Heart valve structure and function in development and disease. Annu. Rev. Physiol. 73:29–46
    [Google Scholar]
  50. 50. 
    Hoffmann AD, Peterson MA, Friedland-Little JM, SA Anderson, Moskowitz IP. 2009. Sonic hedgehog is required in pulmonary endoderm for atrial septation. Development 136:1761–70
    [Google Scholar]
  51. 51. 
    Hoffmann AD, Yang XH, Burnicka-Turek O, Bosman JD, Ren X et al. 2014. Foxf genes integrate Tbx5 and Hedgehog pathways in the second heart field for cardiac septation. PLOS Genet 10:e1004604
    [Google Scholar]
  52. 52. 
    Homsy J, Zaidi S, Shen Y, Ware JS, Samocha KE et al. 2015. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science 350:1262–66
    [Google Scholar]
  53. 53. 
    Houyel L, Bajolle F, Capderou A, Laux D, Parisot P, Bonnet D. 2013. The pattern of the coronary arterial orifices in hearts with congenital malformations of the outflow tracts: a marker of rotation of the outflow tract during cardiac development?. J. Anat. 222:349–57
    [Google Scholar]
  54. 54. 
    Houyel L, Khoshnood B, Anderson RH, Lelong N, Thieulin A-C et al. 2011. Population-based evaluation of a suggested anatomic and clinical classification of congenital heart defects based on the International Paediatric and Congenital Cardiac Code. Orphanet J. Rare Dis. 6:64
    [Google Scholar]
  55. 55. 
    Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Tchervenkov C et al. 2010. Valvular operations in patients with congenital heart disease: increasing rates from 1988 to; 2005. Ann. Thorac. Surg. 90:1563–69
    [Google Scholar]
  56. 56. 
    Jacobs JP, Anderson RH, Weinberg PM, Walters HL, Tchervenkov CI et al. 2007. The nomenclature, definition and classification of cardiac structures in the setting of heterotaxy. Cardiol. Young 17:Suppl. 21–28
    [Google Scholar]
  57. 57. 
    Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM. 2000. Fate of the mammalian cardiac neural crest. Development 127:1607–16
    [Google Scholar]
  58. 58. 
    Jin SC, Homsy J, Zaidi S, Lu Q, Morton S et al. 2017. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat. Genet. 49:1593–601
    [Google Scholar]
  59. 59. 
    Kanani M, Moorman AFM, Cook AC, Webb S, Brown NA et al. 2005. Development of the atrioventricular valves: clinicomorphological correlations. Ann. Thorac. Surg. 79:1797–804
    [Google Scholar]
  60. 60. 
    Kelly RG, Brown NA, Buckingham ME. 2001. The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm. Dev. Cell 1:435–40
    [Google Scholar]
  61. 61. 
    Khoshnood B, Lelong N, Houyel L, Thieulin A-C, Jouannic J-M et al. 2012. Prevalence, timing of diagnosis and mortality of newborns with congenital heart defects: a population-based study. Heart 98:1667–73
    [Google Scholar]
  62. 62. 
    Kim RY, Robertson EJ, Solloway MJ. 2001. Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev. Biol. 235:449–66
    [Google Scholar]
  63. 63. 
    Kirby ML, Gale TF, Stewart DE. 1983. Neural crest cells contribute to normal aorticopulmonary septation. Science 220:1059–61
    [Google Scholar]
  64. 64. 
    Koshiba-Takeuchi K, Mori AD, Kaynak BL, Cebra-Thomas J, Sukonnik T et al. 2009. Reptilian heart development and the molecular basis of cardiac chamber evolution. Nature 461:95–98
    [Google Scholar]
  65. 65. 
    Kramer TC. 1942. The partitioning of the truncus and conus and the formation of the membranous portion of the interventricular septum in the human heart. Am. J. Anat. 71:343–70
    [Google Scholar]
  66. 66. 
    Krishnan A, Samtani R, Dhanantwari P, Lee E, Yamada S et al. 2014. A detailed comparison of mouse and human cardiac development. Pediatr. Res. 76:500–7
    [Google Scholar]
  67. 67. 
    LaHaye S, Lincoln J, Garg V. 2014. Genetics of valvular heart disease. Curr. Cardiol. Rep. 16:487
    [Google Scholar]
  68. 68. 
    Lamers WH, Virágh S, Wessels A, Moorman AF, Anderson RH. 1995. Formation of the tricuspid valve in the human heart. Circulation 91:111–21
    [Google Scholar]
  69. 69. 
    Lamers WH, Wessels A, Verbeek FJ, Moorman AF, Virágh S et al. 1992. New findings concerning ventricular septation in the human heart: implications for maldevelopment. Circulation 86:1194–205
    [Google Scholar]
  70. 70. 
    Le Garrec J-F, Domínguez JN, Desgrange A, Ivanovitch KD, Raphaël E et al. 2017. A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics. eLife 6:e28951
    [Google Scholar]
  71. 71. 
    Lescroart F, Kelly RG, Le Garrec J-F, Nicolas J-F, Meilhac SM, Buckingham M 2010. Clonal analysis reveals common lineage relationships between head muscles and second heart field derivatives in the mouse embryo. Development 137:3269–79
    [Google Scholar]
  72. 72. 
    Lescroart F, Mohun T, Meilhac SM, Bennett M, Buckingham M. 2012. Lineage tree for the venous pole of the heart: clonal analysis clarifies controversial genealogy based on genetic tracing. Circ. Res. 111:1313–22
    [Google Scholar]
  73. 73
    Lescroart F, Wang X, Lin X, Swedlund B, Gargouri S et al. 2018. Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq. Science 359:1177–81
    [Google Scholar]
  74. 74.. 
    Lev M, Bharati S, Meng CC, Liberthson RR, Paul MH, Idriss F. 1972. A concept of double-outlet right ventricle. J. Thorac. Cardiovasc. Surg. 64:271–81
    [Google Scholar]
  75. 75. 
    Li G, Xu A, Sim S, Priest JR, Tian X et al. 2016. Transcriptomic profiling maps anatomically patterned subpopulations among single embryonic cardiac cells. Dev. Cell 39:491–507
    [Google Scholar]
  76. 76. 
    Li QY, Newbury-Ecob RA, Terrett JA, Wilson DI, Curtis AR et al. 1997. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat. Genet. 15:21–29
    [Google Scholar]
  77. 77. 
    Lin AE, Krikov S, Riehle-Colarusso T, Frías JL, Belmont J et al. 2014. Laterality defects in the national birth defects prevention study (1998–2007): birth prevalence and descriptive epidemiology. Am. J. Med. Genet. A 164A:2581–91
    [Google Scholar]
  78. 78. 
    Lincoln J, Alfieri CM, Yutzey KE. 2004. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Dev. Dyn. 230:239–50
    [Google Scholar]
  79. 79. 
    Liu W, Selever J, Wang D, Lu M-F, Moses KA et al. 2004. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. PNAS 101:4489–94
    [Google Scholar]
  80. 80. 
    Liu X, Tobita K, Francis RJB, Lo CW. 2013. Imaging techniques for visualizing and phenotyping congenital heart defects in murine models. Birth Defects Res. C 99:93–105
    [Google Scholar]
  81. 81. 
    Liu X, Yagi H, Saeed S, Bais AS, Gabriel GC et al. 2017. The complex genetics of hypoplastic left heart syndrome. Nat. Genet. 49:1152–59
    [Google Scholar]
  82. 82. 
    Liu Y, Chen S, Zühlke L, Black GC, Choy M-K et al. 2019. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. Int. J. Epidemiol. 48:455–63
    [Google Scholar]
  83. 83. 
    Lopez L, Houyel L, Colan SD, Anderson RH, Béland MJ et al. 2018. Classification of ventricular septal defects for the eleventh iteration of the International Classification of Diseases—striving for consensus: a report from the International Society for Nomenclature of Paediatric and Congenital Heart Disease. Ann. Thorac. Surg. 106:1578–89
    [Google Scholar]
  84. 84. 
    Luna-Zurita L, Prados B, Grego-Bessa J, Luxán G, del Monte G et al. 2010. Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation. J. Clin. Investig. 120:3493–507
    [Google Scholar]
  85. 85. 
    Ma L, Lu M-F, Schwartz RJ, Martin JF. 2005. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development 132:5601–11
    [Google Scholar]
  86. 86. 
    MacGrogan D, Münch J, de la Pompa JL. 2018. Notch and interacting signalling pathways in cardiac development, disease, and regeneration. Nat. Rev. Cardiol. 15:685–704
    [Google Scholar]
  87. 87. 
    Männer J, Seidl W, Steding G. 1993. Correlation between the embryonic head flexures and cardiac development: an experimental study in chick embryos. Anat. Embryol. 188:269–85
    [Google Scholar]
  88. 88. 
    Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache M. 2014. Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010. Circulation 130:749–56
    [Google Scholar]
  89. 89. 
    Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M et al. 2012. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management; a scientific statement from the American Heart Association. Circulation 126:1143–72
    [Google Scholar]
  90. 90. 
    Markwald RR, Fitzharris TP, Manasek FJ. 1977. Structural development of endocardial cushions. Am. J. Anat. 148:85–119
    [Google Scholar]
  91. 91. 
    Meilhac SM, Esner M, Kelly RG, Nicolas J-F, Buckingham ME. 2004. The clonal origin of myocardial cells in different regions of the embryonic mouse heart. Dev. Cell 6:685–98
    [Google Scholar]
  92. 92. 
    Meilhac SM, Esner M, Kerszberg M, Moss JE, Buckingham ME. 2004. Oriented clonal cell growth in the developing mouse myocardium underlies cardiac morphogenesis. J. Cell Biol. 164:97–109
    [Google Scholar]
  93. 93. 
    Merscher S, Funke B, Epstein JA, Heyer J, Puech A et al. 2001. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104:619–29
    [Google Scholar]
  94. 94. 
    Midgett M, Thornburg K, Rugonyi S. 2017. Blood flow patterns underlie developmental heart defects. Am. J. Physiol. Heart Circ. Physiol. 312:H632–42
    [Google Scholar]
  95. 95. 
    Mifflin JJ, Dupuis LE, Alcala NE, Russell LG, Kern CB. 2018. Intercalated cushion cells within the cardiac outflow tract are derived from the myocardial troponin T type 2 (Tnnt2) Cre lineage. Dev. Dyn. 247:1005–17
    [Google Scholar]
  96. 96. 
    Mohapatra B, Casey B, Li H, Ho-Dawson T, Smith L et al. 2009. Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations. Hum. Mol. Genet. 18:861–71
    [Google Scholar]
  97. 97. 
    Mohun TJ, Anderson RH. 2020. 3D anatomy of the developing heart: understanding ventricular septation. Cold Spring Harb. Perspect. Biol. 12:a037465
    [Google Scholar]
  98. 98. 
    Mohun TJ, Brown NA, Anderson RH 2016. Development of the heart and great vessels. Kaufman's Atlas of Mouse Development Supplement: With Coronal Sections R Baldock, J Bard, DR Davidson, G Morriss-Kay 95–109 Boston: Academic
    [Google Scholar]
  99. 99. 
    Moore-Morris T, van Vliet PP, Andelfinger G, Puceat M. 2018. Role of epigenetics in cardiac development and congenital diseases. Physiol. Rev. 98:2453–75
    [Google Scholar]
  100. 100. 
    Moreau JLM, Kesteven S, Martin EMMA, Lau KS, Yam MX et al. 2019. Gene-environment interaction impacts on heart development and embryo survival. Development 146:dev172957
    [Google Scholar]
  101. 101. 
    Morton PD, Ishibashi N, Jonas RA. 2017. Neurodevelopmental abnormalities and congenital heart disease: insights into altered brain maturation. Circ. Res. 120:960–77
    [Google Scholar]
  102. 102. 
    Mostefa-Kara M, Bonnet D, Belli E, Fadel E, Houyel L. 2015. Anatomy of the ventricular septal defect in outflow tract defects: similarities and differences. J. Thorac. Cardiovasc. Surg. 149:682–88.e1
    [Google Scholar]
  103. 103. 
    Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE et al. 2003. Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome. Nat. Genet. 33:407–11
    [Google Scholar]
  104. 104. 
    Niederreither K, Subbarayan V, Dollé P, Chambon P. 1999. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat. Genet. 21:444–48
    [Google Scholar]
  105. 105. 
    Norris DP, Brennan J, Bikoff EK, Robertson EJ. 2002. The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. Development 129:3455–68
    [Google Scholar]
  106. 106. 
    Odelin G, Faure E, Coulpier F, Di Bonito M, Bajolle F et al. 2018. Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve. Development 145:dev151944
    [Google Scholar]
  107. 107. 
    Oosthoek PW, Wenink AC, Vrolijk BC, Wisse LJ, DeRuiter MC et al. 1998. Development of the atrioventricular valve tension apparatus in the human heart. Anat. Embryol. 198:317–29
    [Google Scholar]
  108. 108. 
    Øyen N, Poulsen G, Boyd HA, Wohlfahrt J, Jensen PKA, Melbye M. 2009. Recurrence of congenital heart defects in families. Circulation 120:295–301
    [Google Scholar]
  109. 109. 
    Patten BM. 1922. The formation of the cardiac loop in the chick. Am. J. Anat. 30:373–97
    [Google Scholar]
  110. 110. 
    Peyvandi S, Latal B, Miller SP, McQuillen PS. 2019. The neonatal brain in critical congenital heart disease: insights and future directions. Neuroimage 185:776–82
    [Google Scholar]
  111. 111. 
    Phillips HM, Mahendran P, Singh E, Anderson RH, Chaudhry B, Henderson DJ. 2013. Neural crest cells are required for correct positioning of the developing outflow cushions and pattern the arterial valve leaflets. Cardiovasc. Res. 99:452–60
    [Google Scholar]
  112. 112. 
    Pierpont ME, Brueckner M, Chung WK, Garg V, Lacro RV et al. 2018. Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association. Circulation 138:e653–711
    [Google Scholar]
  113. 113. 
    Ryckebusch L, Wang Z, Bertrand N, Lin S-C, Chi X et al. 2008. Retinoic acid deficiency alters second heart field formation. PNAS 105:2913–18
    [Google Scholar]
  114. 114. 
    Saijoh Y, Oki S, Ohishi S, Hamada H. 2003. Left-right patterning of the mouse lateral plate requires nodal produced in the node. Dev. Biol. 256:160–72
    [Google Scholar]
  115. 115. 
    Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R et al. 1997. TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes. Development 124:2659–70
    [Google Scholar]
  116. 116. 
    Shieh JTC, Bittles AH, Hudgins L. 2012. Consanguinity and the risk of congenital heart disease. Am. J. Med. Genet. A 158A:1236–41
    [Google Scholar]
  117. 117. 
    Shirai M, Imanaka-Yoshida K, Schneider MD, Schwartz RJ, Morisaki T 2009. T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfβ2 expression and endocardial cushion formation. PNAS 106:18604–9
    [Google Scholar]
  118. 118. 
    Shiratori H, Hamada H. 2006. The left-right axis in the mouse: from origin to morphology. Development 133:2095–104
    [Google Scholar]
  119. 119. 
    Sifrim A, Hitz M-P, Wilsdon A, Breckpot J, Turki SHA et al. 2016. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat. Genet. 48:1060–65
    [Google Scholar]
  120. 120. 
    Sigmon ER, Kelleman M, Susi A, Nylund CM, Oster ME. 2019. Congenital heart disease and autism: a case-control study. Pediatrics 144:e20184114
    [Google Scholar]
  121. 121. 
    Sizarov A, Baldwin H, Srivastava D, Moorman AF 2016. Development of the heart: morphogenesis, growth, and molecular regulation of differentiation. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult HD Allen, RE Shaddy, DJ Penny, TF Feltes, F Cetta 1–54 Philadelphia: Wolters Kluwer
    [Google Scholar]
  122. 122. 
    Sizarov A, Lamers WH, Mohun TJ, Brown NA, Anderson RH, Moorman AFM. 2012. Three-dimensional and molecular analysis of the arterial pole of the developing human heart. J. Anat. 220:336–49
    [Google Scholar]
  123. 123. 
    Sizarov A, Ya J, de Boer BA, Lamers WH, Christoffels VM, Moorman AFM. 2011. Formation of the building plan of the human heart: morphogenesis, growth, and differentiation. Circulation 123:1125–35
    [Google Scholar]
  124. 124. 
    Snarr BS, Wirrig EE, Phelps AL, Trusk TC, Wessels A. 2007. A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development. Dev. Dyn. 236:1287–94
    [Google Scholar]
  125. 125. 
    Stottmann RW, Choi M, Mishina Y, Meyers EN, Klingensmith J. 2004. BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium. Development 131:2205–18
    [Google Scholar]
  126. 126. 
    Sugi Y, Ito N, Szebenyi G, Myers K, Fallon JF et al. 2003. Fibroblast growth factor (FGF)-4 can induce proliferation of cardiac cushion mesenchymal cells during early valve leaflet formation. Dev. Biol. 258:252–63
    [Google Scholar]
  127. 127. 
    Sullivan PM, Dervan LA, Reiger S, Buddhe S, Schwartz SM. 2015. Risk of congenital heart defects in the offspring of smoking mothers: a population-based study. J. Pediatr. 166:978–84.e2
    [Google Scholar]
  128. 128. 
    Supp DM, Witte DP, Potter SS, Brueckner M. 1997. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature 389:963–66
    [Google Scholar]
  129. 129. 
    Tang S, Snider P, Firulli AB, Conway SJ. 2010. Trigenic neural crest-restricted Smad7 over-expression results in congenital craniofacial and cardiovascular defects. Dev. Biol. 344:233–47
    [Google Scholar]
  130. 130. 
    Thiene G, Frescura C. 2010. Anatomical and pathophysiological classification of congenital heart disease. Cardiovasc. Pathol. 19:259–74
    [Google Scholar]
  131. 131. 
    Thompson RP, Abercrombie V, Wong M. 1987. Morphogenesis of the truncus arteriosus of the chick embryo heart: movements of autoradiographic tattoos during septation. Anat. Rec. 218:434–40
    [Google Scholar]
  132. 132. 
    Togi K, Yoshida Y, Matsumae H, Nakashima Y, Kita T, Tanaka M. 2006. Essential role of Hand2 in interventricular septum formation and trabeculation during cardiac development. Biochem. Biophys. Res. Commun. 343:144–51
    [Google Scholar]
  133. 133. 
    Tremblay C, Loomba RS, Frommelt PC, Perrin D, Spicer DE et al. 2017. Segregating bodily isomerism or heterotaxy: potential echocardiographic correlations of morphological findings. Cardiol. Young 27:1470–80
    [Google Scholar]
  134. 134. 
    Tsao P-C, Lee Y-S, Jeng M-J, Hsu J-W, Huang K-L et al. 2017. Additive effect of congenital heart disease and early developmental disorders on attention-deficit/hyperactivity disorder and autism spectrum disorder: a nationwide population-based longitudinal study. Eur. Child Adolesc. Psychiatry 26:1351–59
    [Google Scholar]
  135. 135. 
    Tyser RCV, Ibarra-Soria X, McDole K, Arcot Jayaram S, Godwin J et al. 2021. Characterization of a common progenitor pool of the epicardium and myocardium. Science 371:eabb2986
    [Google Scholar]
  136. 136. 
    Van Mierop LH, Gessner IH. 1972. Pathogenetic mechanisms in congenital cardiovascular malformations. Prog. Cardiovasc. Dis. 15:67–85
    [Google Scholar]
  137. 137. 
    Van Praagh R. 1972. The segmental approach to diagnosis in congenital heart disease. Birth Defects Orig. Art. Ser. 8:4–23
    [Google Scholar]
  138. 138. 
    Van Praagh S, Davidoff A, Chin A, Shiel F, Reynolds J, Vanpraagh R 1982. Double outlet right ventricle: anatomic types and developmental implications based on a study of 101 autopsied cases. Coeur 13:390–439
    [Google Scholar]
  139. 139. 
    Van Praagh R, Ongley PA, Swan HJ. 1964. Anatomic types of single or common ventricle in man: morphologic and geometric aspects of 60 necropsied cases. Am. J. Cardiol. 13:367–86
    [Google Scholar]
  140. 140. 
    Waldo KL, Hutson MR, Stadt HA, Zdanowicz M, Zdanowicz J, Kirby ML. 2005. Cardiac neural crest is necessary for normal addition of the myocardium to the arterial pole from the secondary heart field. Dev. Biol. 281:66–77
    [Google Scholar]
  141. 141. 
    Waldo KL, Kumiski DH, Wallis KT, Stadt HA, Hutson MR et al. 2001. Conotruncal myocardium arises from a secondary heart field. Development 128:3179–88
    [Google Scholar]
  142. 142. 
    Waxman JS, Keegan BR, Roberts RW, Poss KD, Yelon D. 2008. Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish. Dev. Cell 15:923–34
    [Google Scholar]
  143. 143. 
    Webb S, Brown NA, Anderson RH. 1998. Formation of the atrioventricular septal structures in the normal mouse. Circ. Res. 82:645–56
    [Google Scholar]
  144. 144. 
    Wessels A, van den Hoff MJB, Adamo RF, Phelps AL, Lockhart MM et al. 2012. Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart. Dev. Biol. 366:111–24
    [Google Scholar]
  145. 145. 
    Ya J, van den Hoff MJ, de Boer PA, Tesink-Taekema S, Franco D et al. 1998. Normal development of the outflow tract in the rat. Circ. Res. 82:464–72
    [Google Scholar]
  146. 146. 
    Yelbuz TM, Waldo KL, Kumiski DH, Stadt HA, Wolfe RR et al. 2002. Shortened outflow tract leads to altered cardiac looping after neural crest ablation. Circulation 106:504–10
    [Google Scholar]
  147. 147. 
    Yotti R, Seidman CE, Seidman JG. 2019. Advances in the genetic basis and pathogenesis of sarcomere cardiomyopathies. Annu. Rev. Genom. Hum. Genet. 20:129–53
    [Google Scholar]
  148. 148. 
    Yu CKH, Teoh TG, Robinson S 2006. Obesity in pregnancy. BJOG 113:1117–25
    [Google Scholar]
  149. 149. 
    Zaffran S, Kelly RG, Meilhac SM, Buckingham ME, Brown NA. 2004. Right ventricular myocardium derives from the anterior heart field. Circ. Res. 95:261–68
    [Google Scholar]
  150. 150. 
    Zaidi S, Brueckner M. 2017. Genetics and genomics of congenital heart disease. Circ. Res. 120:923–40
    [Google Scholar]
  151. 151. 
    Zhang Z, Huynh T, Baldini A. 2006. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development 133:3587–95
    [Google Scholar]
  152. 152. 
    Zhou L, Liu J, Olson P, Zhang K, Wynne J, Xie L 2015. Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle progression for cardiac septation. J. Mol. Cell. Cardiol. 85:1–12
    [Google Scholar]
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