**2. Embryology/genetics**

The interventricular septum (IVS) is composed of the mesenchymal and muscular portions. The ventricular septal growth starts around the fifth week of embryonic

development and involves fusion of different septal components. The atrioventricular endocardial cushions form part of the interventricular septum [4]. The muscular interventricular septum arises from the primary fold or ring and grows upward from the floor of the ventricles towards the already fused endocardial cushions [5]. The outflow tract cushions composed of mesenchymal cells as well as neural crest cells contribute to the septation of the common outflow tract, the semilunar valves and also move downward into the ventricles forming the aortopulmonary septum. By the eighth week of gestation, when the endocardial cushions, muscular septum and aortopulmonary septum fuse, the membranous septum is formed and the ventricular septation is complete [6].

Several theories are currently postulated to determine factors affecting normal cardiac septation. The etiology of ventricular septal defect is heterogenous and may involve environmental and genetic factors, commonly referred to as multifactorial inheritance. Known chromosomal abnormalities such as aneuploidies (e.g. trisomy 21 or trisomy 18) and microdeletions such as DiGeorge syndrome are known to be associated with ventricular septal defects [7]. Single gene defects involving TBX-5 causes Holt Oram syndrome and is characterized by a constellation of birth defects, including ventricular septal defects. Transcription factor encoding genes such as TBX, NKX2–5,GATA4 play an important role in the ventricular septum positioning during cardiogenesis. Other genes that may play a possible role in cardiac septation include GATA6, HOMEX and PLG1 [8].
