The major septa of the heart are formed between the 27th and 37th days of development. One way in which a septum can be formed is by two active and growing mass of tissues approaching each other and fusing. This divides the lumen into two separate canals. The formation of these tissues are called endocardial cushions. The formation depends on synthesis and deposition of extracellular matrix, cell migration and proliferation. Areas in which cushions form there is an increased synthesis of extracellular matrix and that will produce endocardial cell covered protrusions into the lumen. The protrusions develop atrioventricular conotruncal regions. They assist in development of atrial and ventricular septa, atrioventricular canal and valves, and the aortic and pulmonary channels. Due to the location of endocardial cushions defects can cause cardiac malformations such as arterial septal defects, ventricular septal defects, and defects that involve the great vessels such as transposition of the great vessels, common truncus arteriosus and tetralogy of Fallot.
In atrial septal defects there can be a defect in the foramen secundum. This is caused by excessive resorption of septum primum, septum secundum or both. Due to this there is an opening between the right and left atria. Some defects can be tolerated with no sign of clinical symptoms till age 30.
In atrioventricular septal defects one of the clinical consideration is persistent common AV canal. This is caused by a failure of fusion of the dorsal and ventral AV cushions. The common AV canal therefore is never separated between a left and right AV canal. Due to this a large hole can be found in the center of the heart. The tricuspid and mitral valve are represented as one valve instead of two separate ones. There is a left to right shunt of blood from left atrium to right atrium, causing an enlarged right atrium and right ventricle. There is also mitral valve regurgitation, causing an enlarged left atrium and left ventricle. Tricuspid atresia can also occur due to not enough of AV cushion tissue available to form the tricuspid valve. Due to this there is agenesis and there is no communication between the right atrium and right ventricle. It is associated with marked cyanosis and will always be accompanied by, patent formen ovale, intraventricular septal defects, overdeveloped left ventricle, and underdeveloped right ventricle.
Tetralogy of Fallot is a rare condition caused by a combination of four heart defects that are present at birth. These abnormalities, which affect the structures of the heart, cause oxygen-poor blood to flow out of the heart and in to the body. Infants with Tetralogy of Fallot usually have blue skin because they do not have enough oxygenated blood.
Transposition of the great arteries is caused by abnormal neural crest cell migration, such that there is no spiral development of the AP septum. The aorta rises abnormally from the right ventricle and the pulmonary trunk rises abnormally from the left ventricle. Due to this the systemic and pulmonary circuit are completely separate. It is incompatible with life unless a shunt like VSD or Patent ductus arteriosus exists. It is clinically associated with marked cyanosis and right to left shunting of blood.