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cleft lip/palate

Tuesday 9 November 2004

Definition: 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.


- labial clef
- labiopalatal cleft
- nasolabiopalatal cleft


- unilateral cleft lip/palate
- bilateral cleft lip/palate
- anterior medial cleft lip/palate


- sporadic cleft lip - non-syndromic cleft lip
- autosomal dominant nonsyndromic cleft lip/palate
- syndromic cleft lip


- 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

FGF signaling

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

- IRF6
- Van der Woude syndrome


- Cleft lip and palate: understanding genetic and environmental influences. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Nat Rev Genet. 2011 Mar;12(3):167-78. PMID: 21331089

- 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