Cleft lip with or without cleft palate: Reanalysis of a three-generation family study from England

✍ Scribed by Dr. Mary L. Marazita; Alisa M. Goldstein; Susan L. Smalley; M. Anne Spence; D. C. Rao

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 495 KB
• Volume: 3
• Category: Article
• ISSN: 0741-0395
• DOI: 10.1002/gepi.1370030506

✦ Synopsis

The study population consists of 424 three-generation families originally ascertained through nonsyndromic cleft lip with or without cleft palate ( C L k P ) surgical probands by Carter et al [J Med Genet 19:246-261, 19821 in London, England. Carter et al proposed that the multifactorial threshold model (MFIT) could explain the data. The goal of our study was to test that hypothesis, plus alternatives, rigorously.

Two approaches were used: 1) Carter et a1 had proposed that these data were consistent with the predictions of the MF/T as presented by Carter [Br Med Bull 25:52-57, 19691. However, we tested those predictions using standard x2 tests and found statistically significant departures from the predictions in these families.

2. Complex segregation analysis under the mixed model was performed. Again, the MFiT model could be rejected, as could a model of a major locus alone. The best-fitting model included both major locus and multifactorial components. When the data were analyzed in two parts based on the proband's phenotype (CL vs CL+P) there was some evidence of heterogeneity in that there was a significant proportion of sporadic cases in the families of CL probands but not in the families of C L + P probands.

Our results provide no support for the MF/T model. The results from segregation analyses of C L S P in these families were most consistent with autosomal major gene inheritance plus multifactorial contributions.