cleft lip/palate

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.

Topography

 labial clef
 labiopalatal cleft
 nasolabiopalatal cleft

Types

 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

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

Reviews

 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