Aetiological, modifying and lethal factors in cleft lip and palate.

Prenatal factors influencing cleft lip (CL), cleft lip and palate (CLP) and isolated cleft palate (CP) may account for the development of the defect (aetiological factor) for a change in the degree or type of the defect (modifying factor), or for the death of the embryo (lethal factor). Each active factor appears to act in all three directions, all be it at different ratios. This is used for analysis of groups of cleft-effected individuals registered at the Department of Plastic Surgery, Prague, from the catchment area of Bohemia. In terms of cleft defect teratogenesis (aetiology, modification, lethality) a "protective influence" appears probable in female embryos, in blood group A (ABO system), in HLA antigens A9, A11, B35. An "embryotoxic influence" i.e., an increase in all the three influences is seen in male embryos, regional influences, in the B and AB blood groups, in HLA antigens B17, in primiparae, in multiple pregnancies, in older mothers and in cytomegalovirus infections. The Epstein-Barr virus seem to increase, in particular, CLP embryo lethality. The activity of the factors was rated by means of correlations between the cleft frequency in first-degree relatives and the frequency of the factor in six subgroups classified by the cleft defect subtypes, by means of interactions between two and more factors and by a study of the differences between male and female probands. A model of the threshold of CL and CP teratogenesis was proposed, a model in agreement with prenatal reciprocal equilibrium.