CHDs to go undetected throughout life. Some children have no signs while others may exhibit shortness of breath, cyanosis, fainting, heart murmur, under-development of limbs and muscles, poor feeding or growth, or respiratory infections. Congenital heart defects cause abnormal heart structure resulting in production of certain sounds called heart murmur. These can sometimes be detected by auscultation; however, not all heart murmurs are caused by congenital heart defects. Associated conditions Congenital heart defects are associated with an increased incidence of seven other specific medical conditions, together being called the VACTERL association: V — Vertebral anomalies A — Anal atresia C — Cardiovascular anomalies T — Tracheoesophageal fistula E — Esophageal atresia R — Renal (Kidney) and/or radial anomalies L — Limb defects Ventricular septal defect (VSD), atrial septal defects, and tetralogy of Fallot are the most common congenital heart defects seen in the VACTERL association. Less common defects in the association are truncus arteriosus and transposition of the great arteries. Causes The cause of congenital heart disease may be genetic, environmental, or a combination of both. Genetic Genetic mutations, often sporadic, represent the largest known cause of congenital heart defects. They are described in the table below. Molecular pathways The genes regulating the complex developmental sequence have only been partly elucidated. Some genes are associated with specific defects. A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, α-myosin heavy chain (MYH6) are associated with atrial septal defects. Several proteins that interact with MYH6 are also associated with cardiac defects. The transcription factor GATA4 forms a complex with the TBX5 which interacts with MYH6. Another factor, the homeobox (developmental) gene, NKX2-5 also interacts with MYH6. Mutations of all these proteins are associated with both atrial and ventricular septal defects; In addition, NKX2-5 is associated with defects in the electrical conduction of the heart and TBX5 is related to the Holt–Oram syndrome which includes electrical conduction defects and abnormalities of the upper limb. The Wnt signaling co-factors BCL9, BCL9L and PYGO might be part of these molecular pathways, as when their genes are mutated, this causes phenotypes similar to the features present in Holt-Oram syndrome. Another T-box gene, TBX1, is involved in velo-cardio-facial syndrome DiGeorge syndrome, the most common deletion which has extensive symptoms including defects of the cardiac outflow tract including tetralogy of Fallot. The notch signaling pathway, a regulatory mechanism for cell growth