Human congenital anomalies: application of new genetic tools and concepts

The discovery of nontraditional inheritance and of developmental gene families common to all metazoans has revolutionized research on human congenital anomalies. The most gratifying results of these new concepts are summarized in Table 5: several human syndromes have already been related to their causative genes. Classic embryonic mechanisms (ie, gastrulation, segmentation, adhesion) also have been correlated with specific molecules. Perhaps most optimistic are the facts that many of the relevant molecules can be viewed as growth factors and that many anomalies are examples of extended or arrested development known as heterochrony. The implication is that genetic screening and preconceptional diagnosis will allow treatment of congenital malformations by supplementation/suppression of the maternofetal unit. This future specialty of "gestational endocrinology" is already being used for embryonic therapy of 21-hydroxylase deficiency.