<unk>  is inherited as an autosomal dominant disease caused by a mutation in a single gene with equal distribution between the sexes. The disease has high penetrance at about 96% but the phenotypic expression varies from lower lip pits with cleft lip and cleft palate to no visible abnormalities. Approximately 88% of<unk>  patients display lower lip pits, and in about 64% of cases lip pits are the only visible defect. Reported clefting covers a wide range including submucous cleft palate, incomplete unilateral CL, bifid uvula, and complete bilateral CLP.<unk>  is the most common orofacial clefting syndrome, accounting for 2% of CLP cases. The majority of<unk>  cases are caused by haploinsufficiency due to mutations in the interferon regulatory factor 6 gene (IRF6) on chromosome 1 in the 1q32-q41 region known as<unk>  locus 1. A second, less common, causative locus is found at 1p34, known as<unk>  locus 2 <unk> 2). More recent work has shown that GRHL3 is the<unk> 2 gene. Grhl3 is downstream of Irf6 in oral epithelium, suggesting a common molecular pathway leading to<unk> . Prior work also suggested WDR65 as a candidate gene. IRF6 contains two non-coding and seven coding exons and is part of a family of nine transcription factors with a highly conserved helix-turn-helix DNA binding domain called the Smad-interferon regulatory factor binding domain (SMIR). Mutations in coding or non-coding IRF6 exons can result in<unk> . Due to the wide range of expressivity, it is also believed that other unidentified loci contribute to disease development. An example of the clear phenotypic variability is a monozygotic twin study conducted by Jobling et al. (2010). Two monozygotic female twins had the same IRF6 mutation; however Twin A was born with a bilateral cleft lip, whereas Twin B had bilateral lip pits and no orofacial clefting. Both twins were diagnosed with<unk> . The twins' father had lip pits alone and a family history of CLP, CP, CL, and/or lip pits. Both twins were diagnosed with<unk> . Polymerase chain reaction (PCR) amplification was done for all exons of IRF6, and a missense mutation was discovered in exon 4. The tyrosine in the normal protein at this position is conserved across mammals, frogs, and chickens, so despite the fact that it was a previously unreported mutation, it was expected to be deleterious. This study is not the first case of different phenotypes occurring between monozygotic twins. Possible causes of phenotypic variability include variations in the intrauterine environment, epigenetic differences, or chance effects.
Van der Woude syndrome
Helsmoortel-Van der Aa syndrome
Van Den Bosch syndrome
Koolen–De Vries syndrome
Van Wyk and Grumbach syndrome
Wildervanck syndrome
Van Gogh syndrome
Nezelof syndrome