Cleft lip with/without cleft palate (CL/P) is one of the most common birth defects with a prevalence of around 1/700 live birth worldwide. A wide array of genetic and environmental risk factors have been identified in CL/P through genetic and epidemiologic studies. CleftGeneDB is the first comprehensive database for genes associated with CL/P in humans and mice. The CleftGeneDB displays the cleft genes (originally identified in either humans or mice), which are annotated in 10 eukaryotic species, and the information (e.g. network, KEGG, GO, microRNA) from bioinformatic analyses. Thus, the CleftGeneDB can serve as a useful multi-species resource for the study of craniofacial development and craniofacial birth defects. CleftGeneDB will be updated and expanded to the other craniofacial birth defects.
Lip formation begins at embryonic 32 days of gestation in humans, when the surface ectoderm thickens bilaterally on the ventrolateral aspect of the frontonasal process to form the nasal placodes. The maxillary process grows and pushes the nasal pits medially, whereas the ventrolateral growth of the medial nasal process converts the round nasal pits into dorsally pointed slits at 35 days of gestation in humans. The upper lip forms by 48 days of gestation in humans and by embryonic day E12.5 in mice.
Palate formation begins with two primordia, the primary and secondary palates, as early as the 6th week of gestation in humans and at E11.5 in mice. The intermaxillary segment, which is derived from the distal part of the medial nasal processes, starts outgrowing toward the oral cavity to form the primary palate at E12.5 in mice and at the 7th week of gestation in humans. Following initiation and growth of the maxillary process, the palatal shelves, which become the secondary palate, first grow vertically along the lateral sides of the tongue. Around week 7-9 of gestation in humans and E14.0 in mice, the palatal shelves elevate into a horizontal position above the dorsum of the tongue, following the growth of the jaws and descent of the tongue. The fusion between the primary and secondary palates is also completed by E16.5 in mice and by the 12th week of gestation in humans. The palatal shelves are indicated in red.
Mouse cleft lip (CL) and/ or cleft palate (CP) is classified into three groups: cleft lip only (CLO; a.k.a. isolated CL), cleft lip with cleft palate (CLP), and cleft palate only (CPO; a.k.a. isolated CP). CLO is further classified into unilateral and bilateral CL, whereas CPO is classified into complete and partial CP. Partial CP is further classified into cleft in the primary palate (anterior region of the palate), cleft in the secondary palate (majority part of the palate), cleft soft palate (posterior region of the palate), and submucous cleft palate (persistence of MEE or incomplete fusion of palatal processes of maxilla). In humans, cleft lip with/ without cleft palate (CL/P) is the most often used term to describe cleft in face. CL/P includes CLO and CLP. Oral and frontal views with the indicated phenotypes are shown.