Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects, but its etiology is largely unknown. It is very likely that both genetic and environmental factors contribute to this malformation.
Topography
labial clef
labiopalatal cleft
nasolabiopalatal cleft
Type
unilateral cleft lip/palate
bilateral cleft lip/palate
anterior medial cleft lip/palate
Classification
sporadic cleft lip - non-syndromic cleft lip
autosomal dominant nonsyndromic cleft lip/palate
syndromic cleft lip
- cleft lip/palate-ectodermal dysplasia syndrome (CLPED1) (MIM.225000)
- Margarita Island ectodermal dysplasia (MIM.225060)
Etiology
Sporadic cleft lip - non-syndromic cleft lip
- germline mutations in PVRL1 gene (MIM.600644)
- genetic polymorphisms at the IRF6 locus are associated with nonsyndromic CL/P, with stronger association in Asian and South American populations.
- germline mutations in MSX1 gene (MIM.600644)
- locus 18q21.1 (17564975)
syndromic cleft lip
- cleft lip/palate-ectodermal dysplasia syndrome (CLPED1) (MIM.225000)
- germline mutations in PVRL1 gene (MIM.142983)
- Meckel syndrome
Fibroblast growth factor signalling, previously known for its involvement in craniofacial development, is now implicated in the genetic basis of both syndromic and non-syndromic CL/P.
At the same time, an important role in lip and palate development is beginning to emerge for small ubiquitin-like modifier modification, a widely used posttranslational regulatory mechanism. Both of these pathways might interact with environmental risk factors for CL/P.
See also
Reviews
Pauws E, Stanier P. FGF signalling and SUMO modification: new players in the aetiology of cleft lip and/or palate. Trends Genet. 2007 Dec;23(12):631-40. PMID: 17981355
Jugessur A, Murray JC. Orofacial clefting: recent insights into a complex trait. Curr Opin Genet Dev. 2005 Jun;15(3):270-8. PMID: 15917202