The most generally accepted model for cleft lip/palate not associated to specific syndromes has been the one that postulates multifactorial inheritance with a threshold. Recent studies using complex analytical techniques have suggested the existence of a major gene with decreased penetrance in its etiology. Some authors have postulated that only a fraction of all cases of non-syndromic CL (P) would be explained by a single major gene. Other cases may be due to different genes, to environmental agents or to the interaction between them. The present study tests the monogenic inheritance model for CL (P) using segregation analysis in a sample of 211 extended pedigrees collected through CL (P) affected probands. The hypotheses of an autosomic recessive gene was analyzed in 151 sibships (size 2 or more) using "Apert's" method, "maximum likelihood method", "singles method" and "sib's, method" (single incomplete ascertainment). Results obtained do not support the hypotheses of autosomal recessive inheritance. Instead, the hypothesis of an autosomal dominant mode of inheritance with low penetrance is not rejected when analyzing the proportion of normal and affected progeny in certain types of matings in a subsample of 30 extended pedigrees with two or more affected individuals.

The most generally accepted model for cleft lip/palate not associated to specific syndromes has been the one that postulates multifactorial inheritance with a threshold. Recent studies using complex analytical techniques have suggested the existence of a major gene with decreased penetrance in its etiology. Some authors have postulated that only a fraction of all cases of non-syndronmic CL (P) would be explained by a single major gene. Other cases may be due to different genes, to environmental agents or to the interaction between them. The present study tests the monogenic inheritance model for CL (P) using segregation analysis in a sample of 211 extended pedigrees collected through CL (P) affected probands. The hypotheses of an autoscmic recessive gene was analized in 151 sibships (size 2 or more) using "Apert's" method, "maximum likelihood method", "singles method" and "sib's, method" (single incomplete ascertainment). Results obtained do not support the hypotheses of autosomal recessive inheritance. Instead, the hypothesis of an autosomal dominant mode of inheritance with low penetrance is not rejected when analyzing the proportion of normal and affected progeny in certain types of matings in a subsample of 30 extended pedigrees with two or more affected individuals.

Eight cephalometric parameters were determined in individuals affected with cleft lip and cleft palate, their parents and siblings and a sample of normal individuals. No differences were found in males in any group. In contrast, affected females had lower measurements than their female relatives, and these lower latter in turn had measurements than control females. Although differences between groups were significant enough overlap existed and therefore genetic counseling based on these measurements would be uncertain.

The familial association of epilepsy and cleft lip with or without cleft palate (CL (P)) is analyzed assuming both entities share common genetic predisposing factors. The genealogical data stemming from 169 CL (P) probands and 168 epileptic probands yielded information on the prevalence rates of cleft and epileptic relatives. The working hypothesis assumes that the relatives of epileptic and cleft probands should have a greater liability to CL (P) and epilepsy, respectively. The results obtained do not support the hypothesis of an etiologic association given that a greater joint prevalence of epileptic and cleft relatives is only observed when the proband is epileptic and not with a cleft proband. This situation seems to reflect a teratogenic effect of the epileptic genotype which expresses itself in those individuals which simultaneously present a greater liability to cleft.