55 GENETIC ANALYSIS OF FACIAL CLEFTS

Abstract

The study included 1499 families with at least one child affected with cleft lip± palate (CL±p) or cleft palate (CP). The families were ascertained in Southern Poland by multiple selection with probability φ = 0.949 and φ = 0.737, respectively. Complex segregation analysis was applied in an attempt to discriminate between the hypotheses of two alleles from single autosomal locus and that of multifactorial inheritance. The empiric recurrence risk of CL±p and CP equalled: 1.6 ± 0.66 and 0.93 ± 0.75, respectively. The heritability was: 54.8% (CL±p) and 52.8% (CP). The complex segregation analysis of CP did not distinguish between recessive model with incomplete penetrance (x2 = 18.27) and that of multifactorial inheritance ( x2 = 20.38). For CL±p, the most plausible hypothesis ( x2 = 16.86) appeared to be that of dominant inheritance with low penetrance (t = 0.277) and relatively high frequency of phenocopies (x = 0.683). The above models with the lowest x2 were used for computation of more precise recurrence risk figures for genetic counseling. Presented results warrant further investigations on the genetic background of craniofacial anomalies. Future studies should concentrate on the improvement of the method of analysis and on the elimination of genetic heterogeneity of CL±p and CP malformations.