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The genetics of isolated orofacial clefts: from genotypes to subphenotypes
Oral Diseases , 07/06/09

Jugessur A et al. - Orofacial clefts are the most common craniofacial birth defects and one of the most common congenital malformations in humans. They require complex multidisciplinary treatment and are associated with elevated infant mortality and significant lifelong morbidity.

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A Jugessur, 07/06/09

Orofacial clefts are common birth defects in humans. They require complex multidisciplinary treatment and are associated with elevated infant mortality and significant lifelong morbidity. The development of the human face is an exquisitely orchestrated process involving the coordinated growth of multiple, independently derived primordia. Perturbations impacting on the genesis or growth of these primordia may interfere with the proper morphogenesis of facial structures, resulting in clefting of the lip, the primary or secondary palate, or a combination of these sites. A variety of genetic approaches in human populations and animal models have greatly facilitated the search for genes involved in human clefting. In this review, we summarize the most prominent genes for orofacial clefts and place these in the context of developmental pathways that shape the craniofacial complex. We highlight several Mendelian clefting syndromes that have provided valuable clues in identifying genes for the more common, isolated forms of clefting. Finally, we elaborate on a number of potential subclinical characteristics associated with what have previously been diagnosed as ‘isolated’ clefts that may serve as additional markers for identifying individuals or families in whom there may be a greater risk of inheriting a cleft.

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