Congenital heart disease is the result of abnormal development of the heart vessels during fetal life and is the most common heart disease in pediatric patients. The pathogenesis of congenital heart disease is complex and is still inconclusive. However, the prevailing view is that it is the result of the interaction of genetic and environmental factors. Alterations in some genes may lead to the development of congenital heart disease, including some single and multiple gene mutations. 1, single gene mutation causes congenital heart disease: research shows that congenital heart disease is inseparably related to single gene mutation, and congenital heart disease caused by single gene mutation is divided into two types: non-syndromic congenital heart disease and syndromic congenital heart disease. (1) Non-syndromic congenital heart disease manifests as malformations of the cardiovascular system only without congenital anomalies of other systems. Non-syndromic congenital heart disease is mainly related to polygenic inheritance, that is, it is caused by abnormal development of the cardiovascular system due to the combination of genetic and environmental factors during embryonic period, and its heritability is about 55% to 65%. (2) Syndromic congenital heart disease not only has abnormalities of the cardiovascular system, but also is accompanied by other functional abnormalities. Therefore, most of these diseases are manifested as syndromic conditions rather than heart disease alone, and there are about 3% of syndromic congenital heart disease caused by a single gene. 2, polygenic inheritance and congenital heart disease: congenital heart disease is a genetic trait controlled by multiple pairs of non-allelic genes, sometimes also associated with environmental factors, family history, etc. Polygenic inheritance can elaborate congenital heart disease that is different from chromosomal inheritance or single gene mutation. Therefore, polygenic inheritance may be associated with congenital heart disease. However, studies in this area are still relatively few and need to be further explored in depth. Besides genetic factors, viral infections in early pregnancy, altitude, nutritional deficiencies during pregnancy, lesions of the amniotic membrane, fetal stress, early gestational pre-eclampsia, diabetes mellitus, hypercalcemia, the use of radiation and cytotoxic drugs in early pregnancy, and the mother’s advanced age are also risk factors for congenital heart disease in pediatric patients.