Background: Orofacial clefts are common congenital malformations usually characterized by a multifactorial etiology. These heterogeneous defects comprise cleft lip (CL), CL with cleft palate (CL/P), and cleft palate, sometimes observed in recognizable syndromes, with mendelian, chromosomal, or environmental pathogenesis. The Van der Woude syndrome is a mendelian CL/P, accounting for about 2% of all cases and caused by mutations in the interferon regulatory factor 6 (IRF6) gene, located on 1q32.2 chromosome.
Objective: Here, we describe a familial case with a novel IRF6 mutation segregating in the maternal line, displaying a highly intrafamilial variable clinical expression.
Conclusion: This report emphasizes the role of the clinician in recognizing the clinical variability and the genetic heterogeneity of CL/P.