How is the face formed and when it goes wrong: In relation to Cleft Lip/Palate

fozia khan


The normal development of the face relies upon the correct morphogenesis of structures in utero that usually occurs within the first trimester of embryonic life. The face is a very complex structure involving many genes and factors and with it being such a crucial part of life, both physically and aesthetically and therefore mentally, its important for everything to be just right. However, when the normal process doesn’t go to plan this results in dysmorphogenesis, which cleft lip and palate (CLP) is an example of as the lip/palate doesn’t fuse together and the infant is left with a gap. Although the exact cause of CLP is unknown, it is thought to be a mixture of genetics, environment and the teratogens the mothers are exposed to within the environment. This report will demonstrate the normal development of the face for the purpose of understanding how it goes wrong, resulting in CLP. Since there is still a lot to be understood about CLP it will also shed light on recent advances in relating SHH and certain genes as a possible cause for this dysmorphogenesis. The report will also briefly look at the relation of CLP with the genes associated with syndromic and non-syndromic diseases and the different types of CLP. There are many other facial defects that are a result of dysmorphogenesis, however as CLP is one of the most common yet poorly understood facial defect, it will be the main focus of this report.


cleft lip; development

Full Text:

Full text

References (2019). Cleft lip and palate. [online] Available from: [Accessed 18 February 2019]

Hamm J, Robin N. Newborn Craniofacial Malformations. Clinics in Perinatology. 2015;42(2):321-336.

Chang C, Schock E, Billmire D, Brugmann S. Craniofacial Syndromes. Principles of Developmental Genetics. 2015;:654-671.

Alonso N, Raposo-Amaral C. Cleft Lip and Palate Treatment. Pp 25-35 Cham: Springer International Publishing; 2018.

Reference G. Van der Woude syndrome [Internet]. Genetics Home Reference. 2019 . Available from: [Accessed 19 February 2019].

6. Helms J. New insights into craniofacial morphogenesis. Development. 2005;132(5):851-861.

Development of the Face and Palate [Internet]. TeachMeAnatomy. Available from: 2019 [Accessed 19 February 2019].

Chang C, Schock E, Billmire D, Brugmann S. Craniofacial Syndromes. Principles of Developmental Genetics. 2015;:653-676.

Martin E. Concise colour medical dictionary. Oxford, pp 239: Oxford University Press; 2015.

Moore K, Persaud T, Torchia M. The developing human. 9th edition, pp 174-186. Philadelphia, PA: Saunders/Elsevier; 2013

Definition of MESENCHYME. 2019 Available from: [Accessed 22 February 2019].

Sadler T, Langman J. Langman's medical embryology. 12th edition, pp 270, Philadelphia, Pa.: Lippincott Williams & Wilkins; 2012.

Schoenwolf G, Bleyl S, Brauer P, Francis-West P. Larsen's human embryology. 4th ed. Philadelphia, pp 563-570. Pa: Elsevier; 2009. 2019. Available from: [Accessed 1 March 2019].

Agbenorku P. Orofacial Clefts: A Worldwide Review of the Problem. 2019.

Tanaka S, Mahabir R, Jupiter D, Menezes J. Updating the Epidemiology of Cleft Lip with or without Cleft Palate. Plastic and Reconstructive Surgery. 2012;129(3):511e-518e.

Bloomfield V, Liao C. 113: Global Trends in the Rate of Cleft Lip and Palate: Bridging the Gap. Paediatrics & Child Health. 2015;20(5):e75-e75.

Nagase Y, Natsume N, Kato T, Hayakawa T. Epidemiological Analysis of Cleft Lip and/or Palate by Cleft Pattern. Journal of Maxillofacial and Oral Surgery. 2010;9(4):389-395.

Omiya T, Ito M, Yamazaki Y. Disclosure of congenital cleft lip and palate to Japanese patients: reported patient experiences and relationship to self-esteem. BMC Research Notes. 2014;7(1):924.

Shkoukani M, Chen M, Vong A. Cleft Lip – A Comprehensive Review. Frontiers in Pediatrics. 2013;1.

Stuppia L, Capogreco M, Marzo G, La Rovere D, Antonucci I, Gatta V et al. Genetics of Syndromic and Nonsyndromic Cleft Lip and Palate. Journal of Craniofacial Surgery. 2011;22(5):1722-1726.

Harper PS. Oral and craniofacial disorders. In: Practical Genetic. Couseling. 6th ed. London: Arnold Press, 2004:231

Gorlin RJ, Cohen MM, Hennekam RCM. Orofacial clefting syndromes. In: Bobrow M, Harper PS, Scriver C, eds. Syndromes of the Head and Neck. New York: Oxford University Press, 2001: 850-860

Zucchero T, Cooper M, Maher B, Daack-Hirsch S, Nepomuceno B, Ribeiro L et al. Interferon Regulatory Factor 6 (IRF6) Gene Variants and the Risk of Isolated Cleft Lip or Palate. New England Journal of Medicine. 2004;351(8):769-780.

Voigt A, Radlanski R, Sarioglu N, Schmidt G. Lippen-Kiefer-Gaumen-Spalten. Der Pathologe. 2017;38(4):241-247.

Dixon M, Marazita M, Beaty T, Murray J. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews Genetics. 2011;12(3):167-178.

Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genetics (2002) Apr; 61(4):248-56.

Marazita ML, Murray JC, Lidral AC, et al. Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35. Am J Hum Genet 2004;75:161-173

Dixon M, Garner J, Ferguson M. Immunolocalisation of epidermal growth factor (EGF), EGF receptor and transforming growth factor alpha (TGFα) during murine palatogenesis in vivo and in vitro. Anatomy and Embryology. 1991;184(1):83-91.

Tanabe A, Taketani S, Endo-Ichikawa Y, Tokunaga R, Ogawa Y, Hiramoto M. Analysis of the candidate genes responsible for nonsyndromic cleft lip and palate in Japanese people. Clin Sci. 2000;99:105–111

Feng C, Zhang E, Duan W, Xu Z, Zhang Y, Lu L. Association between polymorphism of TGFA Taq I and cleft Lip and/or palate: a meta-analysis. BMC Oral Health. 2014;14(1).

Sull J, Liang K, Hetmanski J, Wu T, Fallin M, Ingersoll R et al. Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms. Human Genetics. 2009;126(3):385-394.

Hozyasz KK, Mostowska A, Surowiec Z, et al. Genetic polymorphisms of GSTM1 and GSTT1 in mothers of children with isolated cleft lip with or without cleft palate. Przegl Lek 2005;62:1019-1022

Lipinski R, Song C, Sulik K, Everson J, Gipp J, Yan D et al. Cleft lip and palate results from Hedgehog signaling antagonism in the mouse: Phenotypic characterization and clinical implications. Birth Defects Research Part A: Clinical and Molecular Teratology. 2010;:NA-NA.

Chiang C, Litingtung Y, Lee E, Young K, Corden J, Westphal H et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature. 1996;383(6599):407-413.

Marcucio RS, Cordero DR, Hu D, Helms JA. Dev. Molecular interactions coordinating the development of the forebrain and face. Biol. 2005 Aug 1; 284(1):48-61

Yu K, Deng M, Naluai-Cecchini T, Glass I, Cox T. Differences in Oral Structure and Tissue Interactions during Mouse vs. Human Palatogenesis: Implications for the Translation of Findings from Mice. Frontiers in Physiology. 2017;8.

Berkowitz S. Cleft Lip and Palate, Diagnosis and Management, 2nd edition, pp 3-12, Berlin: Springer; 2006.


Copyright (c) 2020 fozia khan

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Manchester Open Library:
a partnership between Manchester University Press and The University of Manchester Library