Cleft Lip and Palate; a Comprehensive Review

Congenital cleft-Lip and cleft palate has been the subject of many genetic studies, but until recently there has been no consensus as to their modes of inheritance. In fact, claims have been made for just about every genetic mechanism one can think of. Recently, however, evidence has been accumulating that favors a multifactorial basis for these malformations. Cleft lip and palate (CLP) are birth defects that affect the upper lip and the roof of the mouth. CLP has a multifactorial etiology, comprising both genetic and environmental factors. In this review we discuss the recent data on the etiology of cleft lip and palate. The etiology of CLP seems complex, with genetics playing a major role. Several genes causing syndromic CLP have been discovered. Three of them—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 and popliteal pterygium syndromes, respectively; they are also implicated in nonsyndromic CLP. The nature and functions of these genes vary widely, illustrating the high vulnerability within the craniofacial developmental pathways. The etiological complexity of nonsyndromic cleft lip and palate is also exemplified by the large number of candidate genes and loci. To conclude, although the etiology of nonsyndromic CLP is still largely unknown, mutations in candidate genes have been identified in a small proportion of cases. Determining the relative risk of CLP on the basis of genetic background and environmental influence (including smoking, alcohol use, and dietary factors) will be useful for genetic counseling and the development of future preventive measures. The purpose of the present paper is to present the etiology of cleft lip and cleft palate both the genetic and the environmental factors. It is suggested that the genetic basis for diverse kinds of common or uncommon congenital malformations may very well be homogeneous, whilst, at the same, the environmental basis is heterogeneous.