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Genetics of Orofacial Cleft Birth Defects

  • Clinical Genetics (JM Stoler, Section Editor)
  • Published:
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Abstract

Orofacial cleft birth defects (OFCs) are the most common facial birth defects and among the most common of all birth defects. OFCs can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. Notably, many genes that contribute to the etiology of these disorders, both syndromic and nonsyndromic, have now been identified after decades of research using multiple genetic approaches. The pace of gene identification has significantly increased recently due to advances in sequencing and genotyping technologies. Multiple genome-wide association studies of nonsyndromic OFCs have identified genomic regions that were followed by successful targeted sequencing and functional studies. In addition, other genomic techniques, primarily whole-exome sequencing, have also identified the major genes for many syndromic forms of OFC. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies.

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Acknowledgments

We wish to thank our colleagues for generating the literature contributing to this review and we apologize for being unable to cite all of the relevant papers. This work was supported in part by NIH grants K99-DE025060 and R01-DE016148.

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Authors and Affiliations

  1. Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Suite 500 Bridgeside Point, 100 Technology Dr, Pittsburgh, PA, 15219, USA

    Elizabeth J. Leslie & Mary L. Marazita

  2. Department of Human Genetics, Graduate School of Public Health, and Clinical and Translational Science, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Mary L. Marazita

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  1. Elizabeth J. Leslie
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Correspondence to Mary L. Marazita.

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EJ Leslie and ML Marazita both declare no conflict of interest.

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All studies by EJ Leslie and/or ML Marazita involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

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This article is part of the Topical Collection on Clinical Genetics.

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Leslie, E.J., Marazita, M.L. Genetics of Orofacial Cleft Birth Defects. Curr Genet Med Rep 3, 118–126 (2015). https://doi.org/10.1007/s40142-015-0074-x

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