Down syndrome or trisomy 21 is the most common aneuploidy today. It occurs with a prevalence of 1:770 newborns, more frequently in boys than in girls in the ratio of 3 to 2. There are three types which include trisomy 21 (nondisjunction), translocation and mosaicism. Risk factors include older maternal age, genetic translocation carriers and a positive family history. Dysmorphic features include upslanting palpebral fissures, epicanthic folds, brachycephaly, microcephaly, flat facial profile, concave nasal bones, brachydactyly, clinodactyly of the fifth finger, and transverse palmar crease. Cognitive impairment and psychiatric disorders are among the common features of this syndrome. Numerous malformations, as well as an increased risk for the congenital disease development of various organ systems, such as duodenal stenosis, hearing loss, hypothyroidism and Alzheimer’s disease, are often part of Down syndrome. Congenital heart defects are the most common birth defect. These include ventricular and atrial septal defect, persistent ductus arteriosus, tetralogy of Fallot, pulmonary atresia, transposition of large blood vessels, hypoplastic right and left heart syndrome, total anomalous pulmonary venous return, aortic coarctation, aortic defect and atrioventricular septal defect. AVSD is the most common heart defect in Down syndrome and occurs in 40% of those affected. It is caused by a disruption of physiological development of the endocardial cushions. There is a strong association between AV canal defects and Down syndrome. Prenatal determination of AV canal defect increases the risk of developing Down syndrome. Treatment of congenital heart defects depends on the severity and type of defect, and can be conservative and invasive. Numerous defects require only further monitoring.