Are oral clefts a consequence of maternal hormone imbalance? Evidence fromthe sex ratios of sibs of probands

Background: The causes of oral clefts (cleft lip with or without cleft pala te, CL/P, and cleft palate alone, CP) have not been established. However, m aternal intrauterine hormone profiles have been suspected of being involved . There is now substantial evidence that maternal hormone concentrations ar ound the time of conception partially control the sexes of offspring. It is possible that the hormone profiles that control sex of offspring share fea tures of the profiles suspected of causing clefts. This can be tested by ex amining the sex ratios (proportions male) of the unaffected sibs of proband s. If these sex ratios are skewed in the same direction as that of probands , that suggests, ex hypothesi, maternal hormonal involvement in the causati on of clefts. Methods: Accordingly, a search was made for data on the sex ratios of the u naffected sibs of probands with clefts. For reasons given in the text, this search was informal rather than based on electronic data retrieval systems . Nine papers were located giving sex ratios of sibs of probands with CL/P and CP. Results: Published data suggest that the sibs of probands with CL/P have a significantly higher sex ratio than the sibs of probands with CP. Thus the sib sex ratios are skewed in the same direction as those of the probands th emselves. In other words, parents (mothers) of CL/P patients apparently hav e a tendency to produce boys, and parents of CP patients to produce girls. Conclusion: Accordingly, it is suggested that maternal hormone profiles may partially explain the unusual sex ratios (of probands and their sibs), as well as the malformations. (C) 2000 Wiley-Liss, Inc.