Clustering of malformations in the families of South American oral cleft neonates

Abstract

The relatives of 741 newborn children with non-syndromic cleft lip with or without cleft palate (CL +/- P), of 115 with isolated cleft palate (CP), and of equal numbers of appropriate controls were screened for the presence of the same or different malformations. The main findings were as follows. (1) The frequency of familial cases of CL +/- P (17.3%) was much higher than the prevalence of this malformation among the relatives of controls (0.5%). (2) The sibs of CL +/- P subjects showed a higher prevalence of this condition than their parents (2.9% v 1.6%). (3) The degree of genetic determination of this condition should be high (70 to 74%), and the data in general favour a multifactorial model of inheritance, with different thresholds between sexes. However, the action of dominant genes cannot be excluded since selection or dominant genes or both could be postulated to explain the parent/sib difference. (4) The frequency of other malformations was also significantly raised in the families of CL +/- P probands, as compared to controls (12.1% v 6.2%). (5) The prevalence of these other malformations was higher among sibs (1.6%) than parents (0.7%) of CL +/- P babies. (6) A general susceptibility to malformations and different exposure to selective agents may explain these latter findings. (7) None of the comparisons involving CP children yielded significant results.