Some Isolated Cardiac Malformations Can Be Related to Laterality Defects

Abstract

Human beings are characterized by a left⁻right asymmetric arrangement of their internal organs, and the heart is the first organ to break symmetry in the developing embryo. Aberrations in normal left⁻right axis determination during embryogenesis lead to a wide spectrum of abnormal internal laterality phenotypes, including situs inversus and heterotaxy. In more than 90% of instances, the latter condition is accompanied by complex and severe cardiovascular malformations. Atrioventricular canal defect and transposition of the great arteries—which are particularly frequent in the setting of heterotaxy—are commonly found in situs solitus with or without genetic syndromes. Here, we review current data on morphogenesis of the heart in human beings and animal models, familial recurrence, and upstream genetic pathways of left⁻right determination in order to highlight how some isolated congenital heart diseases, very common in heterotaxy, even in the setting of situs solitus, may actually be considered in the pathogenetic field of laterality defects.

Keywords: atrioventricular canal defect; congenital heart disease; genetics; heterotaxy; transposition of the great arteries.

Figure 1

The diagram shows the complete form of AVCD with an ostium primum atrial septal defect, a ventricular septal defect, and a single common atrioventricular valve. The yellow arrows represent the left-to-right shunt through atrial and ventricular septal defects. RA: right atrium; RV: right ventricle; LA: left atrium; CV: common valve; LV: left ventricle; Ao: aorta; PA: pulmonary artery.

Figure 2

Diagram of TGA with ventriculo-arterial discordance and without spiralization of the great arteries. RA: right atrium; RV: right ventricle; LA: left atrium; LV: left ventricle; Ao: aorta; PA: pulmonary artery.