An update on the aetiology of orofacial clefts.
OBJECTIVE
To review recent data on the aetiology of cleft lip and palate.


METHODS
MEDLINE literature search (1986-2003).


METHODS
Literature and data on aetiology of cleft lip and palate using the following key words: 'cleft lip', 'cleft palate', 'aetiology', and 'genetics'.


METHODS
Relevant information and data were reviewed by the authors.


RESULTS
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/palate-ectodermal 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.
Wong
F K
FK
Faculty of Dentisty, The University of Hong Kong, Pokfulam Road, Hong Kong. funwon@netvigator.com
Hagg
U
U
D000428:Alcohol Drinking; D015815:Cell Adhesion Molecules / Q000235:genetics; D002874:Chromosome Mapping; D002971:Cleft Lip / Q000196:embryology / Q000209:etiology*; D002972:Cleft Palate / Q000196:embryology / Q000209:etiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors; D051957:MSX1 Transcription Factor; D000075983:Nectins; D012907:Smoking / Q000009:adverse effects; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; C000619010:NECTIN1 protein, human; D000075983:Nectins; D020825:T-Box Domain Proteins; C416943:TBX22 protein, human; D014157:Transcription Factors