Welcome to Francis Academic Press

Frontiers in Medical Science Research, 2020, 2(2); doi: 10.25236/FMSR.2020.020202.

Etiology of Atrial Septal Defect: Review


Jiang Tianxiao

Corresponding Author:
Jiang Tianxiao

Medical University of Lublin, Poland, 20-059


Atrial septal defect is caused by malformation of the septum between left and right atrium. This paper will firstly review the embryology and classification of atrial septal defect, then the etiology of atrial septal defect will be discussed according to various studies. Even atrial septal defects are treatable, the underlying cause of such defects is not clear, therefore, the research into them must be continued.


Atrial septal defect, Ostium primum, Ostium secundum, Sinus venosus, Unroofed coronary sinus, Tbx5

Cite This Paper

Jiang Tianxiao. Etiology of Atrial Septal Defect: Review. Frontiers in Medical Science Research (2020) Vol. 2 Issue 2: 8-15. https://doi.org/10.25236/FMSR.2020.020202.


[1] Malm, H (2012). Prenatal exposure to selective serotonin reuptake inhibitors and infant outcome. Therapeutic drug monitoring, vol.34, no.6, pp.607-14
[2] Anderson, R.H., Brown, N.A., Webb, S (2002). Development and structure of the atrial septum. Heart. no.88, pp.104-110.
[3] Waller, D.K., Keddie, A.M., Canfield, M.A, et al (2001). Do infants with major congenital anomalies have an excess of macrosomia? Teratology, no.64, pp.311-317.
[4] Webb, G., Gatzoulis, M.A (2006). Atrial septal defects in the adult: recent progress and overview. Circulation, no.114, pp.1645-1653.
[5] Rojas, C.A., Sherief, A., Medina, H.M., et al (2010). Embryology and developmental defects of the interatrial septum. AJR Am J Roentgenol, vol.195, no.5, pp.1100
[6] Rao, P. S (2012). Atrial Septal Defect - A Review. Atrial Septal Defect.
[7] Oliver, J.M., Gallego, P., Gonzalez, A., et al (2002). Sinus venosus syndrome: atrial septal defect or anomalous venous connection? A multiplane transoesophageal approach. Heart, no.88, pp.634-638
[8] Van Praagh, S., Carrera, M.E., Sanders, S.P., et al (1994). Sinus venosus defects: unroofing of the right pulmonary veins-anatomic and echocardiographic findings and surgical treatment. Am Heart J, no.128, pp.365-379
[9] Kallen, K (1999). Maternal smoking and congenital heart defects. Eur J Epidemiol, no.15, pp.731-737.
[10] Ootaki, Y., Yamaguchi, M., Yoshimura, N., et al (2003). Unroofed coronary sinus syndrome: diagnosis, classification, and surgical treatment. J Thorac Cardiovasc Surg, no.126, pp.1655-1656
[11] Malik, S., Cleves, M.A., Honein, M.A., et al (2008). Maternal smoking and congenital heart defects. National Birth Defects Prevention Study. Pediatrics, vol.121,no.4, pp.e810-6
[12] Goetz, S.C., Brown, D.D., Conlon, F.L (2006). TBX5 is required for embryonic cardiac cell cycle progression. Development, vol.133, no.13, pp.2575-2584
[13] Camarata, T., Kremery, J., Snyder, D., et al. (2010). Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish beart atrio-ventricular boundary and valve formation. Dev Biol, vol.337, no.2, pp.233-245.
[14] Holt, M., Oram, S (1960). Familial heart disease with skeletal malformations. Br Heart J, no.22, pp.236-242.
[15] Li, Q.Y., Newbury-Ecob, R.A., Terrett, J.A., et al (1997). Holt–Oram syndrome is caused by mutationsin TBX5, a member of the Brachyury (T) gene family. Nat Genet, no.15, pp.21-29.
[16] Schott JJ, Benson DW, Basson CT, Pease W,  et al (1998). Congenital heart disease caused by mutations in the transcription factor nkx2-5. Science, no.281, pp.108-111.
[17] Loffredo, C.A., Wilson, P.D., Ferencz, C. (2001). Maternal diabetes: An independent risk factor for major cardiovascular malformations with increased mortality of affected infants. Teratology, no.64, pp.98-106.
[18] Xin, N., Qiu, G.R., Gong, K.G., et al (2009). The mechanism of TBX5 abnormal expression in simple congenital heart disease. Yi Chuan, vol.31, no.4, pp.374-380.
[19] Watkins, M., Rasmussen, S., Honein, M., et al (2003). Maternal obesity and risk for birth defects. Pediatrics, vol. 111, no. 5, pp.12-13.
[20] Watkins, M.L., Botto, L.D. (2001). Maternal prepregnancy weight and congenital heart defects in offspring. Epidemiology, no.12, pp.439-446.
[21] Garg, V., Kathiriya, I.S., Barnes, R., Schluterman, et al (2003). GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature, no.424, pp.443-447
[22] Okubo, A., Miyoshi, O., Baba, K., Takagi, M, et al (2004) A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family. J Med Genet, no. 41, pp. 97-98.
[23] Nadeau M, Georges RO, Laforest B, et al (2010). An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proc Natl Acad Sci USA, no.107, pp.19356-19361.
[24] Botto, L.D., Correa, A., Erickson, J.D. (2001) Racial and temporal variations in the prevalence of heart defects. Pediatrics.
[25] Ferencz, C., Loffredo, C., Correa-Villasenor, A., et al (1997) Genetic and environmental risk factors of major cardiovascular malformations: The Baltimore-Washington infant study 1981-1989. Future Publishing Company Inc., Bath.
[26] Forrester, M, Merz, R (2004). Descriptive epidemiology of selected congenital heart defect, Hawaii, 1986-1999. Paediatric and Perinatal Epidemiology, no.18, pp.415-424.
[27] Levy, H.L., Guldberg, P., Guttler, F., Hanley, W.B., et al (2001). Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. Pediatr Res, no.49, pp.636-642.
[28] Nadeau M, Georges RO, Laforest B, et al. (2010). An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proc Natl Acad Sci USA, no.107, 19356-19361.
[29] [Vereczkey, A., Kosa Z., Csaky-Szunyogh, M, et al (2012). Birth outcomes of cases with isolated atrial septal defect type II - a population-based case-control study. Acta Obstet Gynecol.
[30] Samanek, M (1994). Boy:girl ratio in children born with different forms of cardiac malformation: a population-based study. Pediatr Cardiol, no.15, pp.53-57.
[31] Vrijheid, M., Dolk, H., Stone, D (2000). Socioeconomic inequalities in risk of congenital anomaly. Arch. Dis. Child, no.82, pp.349-352.
[32] Tandon, A., Sengupta, S., Shukla, V., et al (2010). Risk Factors for Congenital Heart Disease (CHD) in Vellore. Current Research Journal of Biological Sciences, vol. 2, no. 4, pp.253-258.
[33] Rothman, K.J., Fyler, D.C (1976). Sex, birth order, and maternal age characteristics of infants with congenital heart defects. Am J Epidemiol, no.104, pp.527-534.
[34] [Mastroiacovo, P., Castilla, E.E., Arpino, C., Botting, B., et al (1999). Congenital malformations in twins: an international study. Am J Med Genet, no.83, pp. 117-124.
[35] Becker, S.M., Al Halees, Z., Molina, C., et al (2001). Consanguinity and congenital heart disease in Saudi Arabia. Am J Med Genet, no.99, pp.8-13.