title: Are oral clefts a consequence of maternal hormone imbalance? evidence from the sex ratios of sibs of probands.
abstract: BACKGROUND
  The causes of oral clefts (cleft lip with or without cleft palate, CL/P, and cleft palate alone, CP) have not been established. However, maternal intrauterine hormone profiles have been suspected of being involved. There is now substantial evidence that maternal hormone concentrations around the time of conception partially control the sexes of offspring. It is possible that the hormone profiles that control sex of offspring share features of the profiles suspected of causing clefts. This can be tested by examining the sex ratios (proportions male) of the unaffected sibs of probands. If these sex ratios are skewed in the same direction as that of probands, that suggests, ex hypothesi, maternal hormonal involvement in the causation of clefts.
  
  
  METHODS
  Accordingly, a search was made for data on the sex ratios of the unaffected 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 themselves. In other words, parents (mothers) of CL/P patients apparently have a tendency to produce boys, and parents of CP patients to produce girls.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Galton Laboratory, University College London, London NW1 2HE, England.
authors.forename: W H
authors.initials: WH
authors.lastname: James
mesh_terms: D002971:Cleft Lip / Q000235:genetics* / Q000378:metabolism; D002972:Cleft Palate / Q000235:genetics* / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D008297:Male; D011247:Pregnancy; D012744:Sex Ratio
chemical_list: D012739:Gonadal Steroid Hormones