Predisposing factors to formation of cleft lip and palate: inherited craniofacial skeletal morphology

Abstract

Objective: To identify inherited craniofacial morphologic features in individuals at high risk for cleft of the lip, cleft palate, or both.

Subjects: Twins without cleft from 33 pairs of monozygotic twins discordant for cleft lip, cleft palate, or both were studied. There were 17 males and 16 females of Caucasian origin, ranging from 3 to 18 years (15 with cleft lip and palate [CLP], 10 with cleft lip [CL], and 8 with cleft palate [CP]), collected from five craniofacial centers (United States and Canada).

Design: The twin without cleft (noncleft) from each set was compared with an age- and sex-matched control individual from the Burlington Growth Centre, Toronto, Ontario. Posteroanterior and lateral cephalograms were traced and digitized using a computer custom analysis. Descriptive statistics, Student's t tests, and analysis of variance were used to test 40 variables in a pilot study comparing the noncleft twin groups with the controls. Preliminary analysis permitted pooling of the CLP and CL groups (n = 25). To minimize false-positive significance, only 14 variables (from the maxillofacial area) were tested.

Results: Using the raw probabilities, eight variables showed significant differences between the pooled noncleft CLP and CL (CL[P]) twin group and the controls. However, when the level of significance was adjusted, only four (nasal width [p < .01], cranial base length [p < .05], cranial base width/length ratio [p < .001], and maxillary width/length ratio [p < .05]) were significantly different. No significant differences were confirmed between the noncleft CP twin group and the controls.

Conclusions: The noncleft member of a discordant monozygotic pair has a number of facial characteristics that differ from the general population. These may predispose to the formation of a cleft lip or palate and may result from a deficiency or distortion of the mesenchyme that forms the craniofacial structures.