The source of developmental anomalies lies within deviations from the normal pathways of embryogenesis.

Early stages ofembryonic development can be studiedby identification of developmental genes and their products, using in situhybridization and immuno chemistry and computerized three-dimensional reconstruction of aborted sectioned human embryos.

OROFACIAL CLEFTS

The most frequent craniofacial anomalies are clefts of the upper lip and palate that can now be diagnosed prenatally.

Cleft Lip

Clefts of the lip and palate are among the most common congenital anomalies, occurring in ±1.7 per 1,000 births in Asians, approximately 1 per 1,000 Caucasian births, and approximately 1 per 2,500 births in those of African lineage (Figures 14.1 to 14.5 and Tables 14.1 and 14.2). The frequency of cleft lip /palate is highest in Native Americans, occurring in over 3.6 per 1,000 births and showing a 2:1 female-to-male frequency. Unilateral cleft lips are more frequent on the left than the right and are least frequent bilaterally in the respective ratios of 6:3:1. Isolated cleft palate is distinguished from combined cleft lip and palate; the former occurs about twice as frequently as the combination. Some 2050% of cleft palates are associated with other anomalies. About 5% of facial clefting is syndromic, with over 250 cleft-associated syndromes.

Pathology of Cleft Lip. If the embryo is examined shortly after Carnegie Stage 18 and autolysis is severe, the newly fused tissue may degenerate and an artifactual cleft may appear. Thus, cleft lip cannot be diagnosed in a severely autolyzed embryo.