Genetics and embryological mechanisms of congenital heart diseases.

Developmental genetics of congenital heart diseases has evolved from analysis of embryo sections towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Lineage analysis, transgenic animal models and retrospective clonal analysis of the developing heart led to identification of different cardiac lineages and their respective roles. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population based analysis to screening for mutations in candidates genes identified in animal models. Based on these new concepts, genetic counselling in congenital heart diseases is based on the mechanism of a given heart defect rather than on its anatomy. Using this approach, genetic heterogeneity or intrafamilial variability of a molecular anomaly can at least be partially explained. Close cooperation between molecular embryologists, pathologists involved in heart development and paediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects.