Cleft lip and palate (CLP) is a congenital anomaly characterized by the inappropriate fusion of the upper lip, alveolus, and secondary palate. This study investigated whether expression of interferon regulatory fac tor 6 (IRF6), receptor-like tyrosine kinase (RYK), and paired-box 9 (PAX9), which are essential for the normal development and morphogenesis of craniofacial structures, is dysregulated in children with CLP. Oral mucosa tissue samples were obtained from patients with complete bilateral (CB) CLP (n= 19) during corrective plastic surgery and unaffected control subjects (n= 7). IRF6, RYK, and PAX9 expression was assessed by immunohistochemistry, and data were analyzed with the Mann-Whitney test. In patients, IRF6 immunoreactivity in the connective tissue was moderate to high, but the overall number of IRF6-positive oral epithelial cells was lower than that in controls (z= -3.41; P= 0.01). RYK expression was observed only sporadically in the oral epithelium of 4 patients, in contrast to the control group (z= -3.75; P< 0.001). PAX9-positive epithelial cells were present in low to moderate numbers in patients with CBCLP, while an abundance of these cells was observed in the basal layer of the oral epithelium in controls (z= -3.60; P<0.001). IRF6 is the main connective tissue regulatory factor in CBCLP, and its low level of expression in the oral epithelium suggests a reduced potential for epitheliocyte differentiation, while low PAX9 and RYK expression may explain the decreased cell migration and cleft remodeling in CBCLP.

KEY WORDS: Cleft palate; Interferon regulatory factor 6; Receptor-like tyrosine kinase; Paired box gene 9.