OBJECTIVE. To review recent data on the aetiology of cleft lip and palate.

DATA SOURCES. MEDLINE literature search (1986-2003).

STUDY SELECTION. Literature and data on aetiology of cleft lip and palate using the following key words: ‘cleft lip’, ‘cleft palate’, ‘aetiology’, and ‘genetics’.

DATA EXTRACTION. Relevant information and data were reviewed by the authors.

DATA SYNTHESIS. Cleft lip and palate is one of the most common types of congenital malformation. The aetiology seems complex, but genetics plays a major role. Recently several genes causing syndromic cleft lip and palate have been discovered. Three of them—namely T-box transcription factor-22 (TBX22), poliovirus receptor like-1 (PVRL1), and interferon regulatory factor-6 (IRF6)—are responsible for causing X-linked cleft palate, cleft lip/palateectodermal dysplasia syndrome, and Van der Woude’s and popliteal pterygium syndromes, respectively; they are also implied in non-syndromic cleft lip and palate. The nature and function of these genes vary widely, illustrating high vulnerability within the craniofacial developmental pathways. The aetiological complexity of non-syndromic cleft lip and palate is also exemplified by the large number of candidate genes and loci.

CONCLUSIONS. The aetiology of non-syndromic cleft lip and palate is still largely unknown, but mutations in candidate genes have already been identified in a small proportion of cases of non-syndromic cleft lip and palate. Determining the relative risk of cleft lip and palate, on the basis of genetic background and environmental influence, including smoking, alcohol use, and dietary factors, will aid in genetic counselling and the development of future preventive measures.

Key words: Cleft lip; Cleft palate; Genetics; Mutation; Syndrome

View this abstract indexed in MEDLINE: