Several studies had demonstrated an association between facial shape in parents and the presence of oral clefts in their offspring. It was assumed that facial shape was one predisposing component among many in a multifactorial model of inheritance. ... Several studies had demonstrated an association between facial shape in parents and the presence of oral clefts in their offspring. It was assumed that facial shape was one predisposing component among many in a multifactorial model of inheritance. By cephalometric analysis of a large family with 5 generations of affected individuals, Ward et al. (1994) concluded that facial shape can be used to identify presumed carriers of a major gene associated with an increased risk for oral clefts. Discriminant function analysis indicated that at-risk individuals could be recognized through a combination of increased midfacial and nasal cavity widths, reduced facial height, and a flat facial profile. The use of this approach in providing critical information needed in the search for molecular markers that segregate with the genetic risk for clefting was emphasized. Using quantitative MRI analysis, Nopoulos et al. (2002) compared the brain morphology of adult males with nonsyndromic cleft lip and/or cleft palate with matched healthy controls. They found that subjects with nonsyndromic cleft lip and/or palate had significant abnormalities in brain morphology, consisting of abnormally enlarged anterior regions of the cerebrum, and decreased volumes of the posterior cerebrum and cerebellum. Overall, the most severely affected region was the left temporal lobe. Neiswanger et al. (2007) noted that the spectrum of severity in visible CL/P is broad, ranging from notches of the vermilion and/or grooves in the philtrum to complete unilateral and bilateral clefts of the lip and palate. Minimal or microform expressions of the CL/P phenotype, typically involving subtle defects of the lip, alveolar arch, and/or inferior nasal region, are at the mild end of the spectrum. Using high-resolution ultrasonography to examine the orbicularis oris muscle, Neiswanger et al. (2007) found that 10.3% of 525 noncleft relatives of patients with nonsyndromic cleft lip had discontinuity of the orbicularis oris muscle compared to 5.8% of 257 controls (p = 0.04). Male relatives had a significantly higher rate of discontinuity than male controls (12.0% vs 3.2%; p = 0.01); female relatives also had a higher rate of discontinuity than female controls, but the increase was not statistically significant. These data confirm the hypothesis that subepithelial defects in the orbicularis oris are a mild manifestation of the cleft lip phenotype. Neiswanger et al. (2009) analyzed lip prints from more than 450 individuals, including CL/P patients, their family members, and controls, from the United States, Argentina, and Hungary. Whether using a narrow or broad definition of lower-lip whorl, whorls were associated with CL/P. Under a narrow definition, the frequency of whorls in the US sample was significantly elevated in CL/P patients and their unaffected relatives compared to controls (p = 0.003 and 0.001, respectively), but whorl frequencies did not differ significantly between CL/P patients and their noncleft relatives. In the Argentinian sample, CL/P patients had significantly more whorls than their unaffected family members (p = 0.04, for narrow or broad definition of lower-lip whorl); unrelated Argentinian controls were not available. None of the participants from Hungary had a definite whorl on their lower lip. Neiswanger et al. (2009) suggested that whorl lip print patterns might be part of an expanded phenotypic spectrum of nonsyndromic CL/P.
In 3 patients with cleft lip/palate who had balanced translocations involving 6p and had previously been studied by Davies et al. (1995), Davies et al. (2004) refined the breakpoint regions and identified 2 positional candidate genes, TFAP2A (107580) ... In 3 patients with cleft lip/palate who had balanced translocations involving 6p and had previously been studied by Davies et al. (1995), Davies et al. (2004) refined the breakpoint regions and identified 2 positional candidate genes, TFAP2A (107580) and OFCC1 (614287). Breakpoints in the 3 patients were within 375 to 930 kb of the 5-prime end of the TFAP2A gene, suggesting that they might interfere with regulatory elements. In addition, breakpoint mapping in 1 of the patients indicated that the translocation disrupted the OFCC1 gene in intron 3, potentially abolishing full-length transcription of the gene from the translocated chromosome; in the other 2 patients, the breakpoints were relatively close to the 3-prime end of the gene, suggesting the possibility of position effects.
Murray et al. (1997) reported the results of epidemiologic studies of CL/P ascertained from 6 sites within the Philippines between 1989 and 1996. The findings included a birth prevalence of 1.94 per 1,000 live births for CL/P. Recurrence ... Murray et al. (1997) reported the results of epidemiologic studies of CL/P ascertained from 6 sites within the Philippines between 1989 and 1996. The findings included a birth prevalence of 1.94 per 1,000 live births for CL/P. Recurrence rates in sibs for nonsyndromic CL/P were 23 per 1,000 for cleft lip with or without cleft palate and 14 per 1,000 for cleft palate only. The percentage of clefts associated with multiple congenital anomalies was 21% at birth and 6% for individuals examined during the screening process. These results indicated a high postnatal death rate. The data suggested a high incidence of cleft lip and palate in native-born Filipinos.