Skip to main content
SpringerLink
Log in
Book cover

Prenatal Diagnosis of Orofacial Malformations pp 9–17Cite as

The Genetics of Facial Cleft

  • Chapter
  • First Online:

  • 726 Accesses

Abstract

Cleft lip ± cleft palate (CL/P) and cleft palate (CP) are the most common congenital craniofacial abnormalities with an estimated prevalence of 1:690 in the USA [1]. Both conditions can be divided into syndromic (associated with other abnormalities) and non-syndromic (isolated) with about 70 % of the cases with CL/P and 50 % of the cases with CP being non-syndromic [2]. In the USA, the prevalence of isolated cleft lip (CL) is 1:3226 live births, of isolated cleft lip and palate (CL + CP) 1:1786, and of isolated CP 1:1695 live births [1]. While the prevalence of CP is the same in different countries and ethnic backgrounds, the incidence of CL/P differs according to the race, ethnic background environmental exposures, socioeconomic status, and geographical origin. Thus, in the USA the prevalence of isolated CL/P is lowest among blacks and highest among American Indians. CL/P is also very high among the First Nations population in British Columbia, Canada [1/300] [3]. Furthermore, while CP is more common in females, CL/P is more common in males.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Mai CT, Cassell CH, Meyer RE, Isenburg J, Canfield MA, Rickard R, Olney RS, Stallings EB, Beck M, Hashm SS, et al. Birth defects data from population‐based birth defects surveillance programs in the United States, 2007 to 2011: highlighting orofacial clefts. Birth Defects Res A Clin Mol Teratol. 2014;100:895–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shi M, Wehby GL, Murray JC. Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects. Birth Defects Res C Embryo Today Rev. 2008;84:16–29.

    Article  CAS  Google Scholar 

  3. Lowry RB, Johnson CY, Gagnon F, Little J. Segregation analysis of cleft lip with or without cleft palate in the First Nations (Amerindian) people of British Columbia and review of isolated cleft palate etiologies. Birth Defects Res A Clin Mol Teratol. 2009;85:568–73.

    Article  CAS  PubMed  Google Scholar 

  4. Som PM, Naidich TP. Illustrated review of the embryology and development of the facial region, part 2: late development of the fetal face and changes in the face from the newborn to adulthood. AJNR Am J Neuroradiol. 2014;35:10–8.

    Article  CAS  PubMed  Google Scholar 

  5. Young DL, Schneider RA, Hu D, Helms JA. Genetic and teratogenic approaches to craniofacial development. Crit Rev Oral Biol Med. 2000;11:304–17.

    Article  CAS  PubMed  Google Scholar 

  6. Lu XC, Yu W, Tao Y, Zhao PL, Li K, Tang LJ, Zheng JY, Li L. Contribution of transforming growth factor α polymorphisms to nonsyndromic orofacial clefts: a HuGE review and meta-analysis. Am J Epidemiol. 2014;179:267–81.

    Article  PubMed  Google Scholar 

  7. Lidra AC, Romitti PA, Basart AM, Doetschman T, Leysens NJ, Daack-Hirsch S, Semina EV, Johnson LR, Machida J, Burds A, et al. Association of MSX1 and TGFB3 with nonsyndromic clefting in humans. Am J Hum Genet. 1998;63:557–68.

    Article  Google Scholar 

  8. Blanton SH, Cortez A, Stal S, Mulliken JB, Finnell RH, Hecht JT. Variation in IRF6 contributes to nonsyndromic cleft lip and palate. Am J Med Genet A. 2005;37A:259–62.

    Article  Google Scholar 

  9. van Rooij IALM, Swinkels DW, Blom HJ, Merkus HMWM, Steegers-Theunissen RPM. Vitamin and homocysteine status of mothers and infants and the risk of nonsyndromic orofacial clefts. Am J Obstet Gynecol. 2003;189:1155–60.

    Article  PubMed  Google Scholar 

  10. Hunt S, Russel A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J, et al. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology. 2008;71:272–6.

    Article  CAS  PubMed  Google Scholar 

  11. Hyoun SC, Običan SG, Scialli AR. Teratogen update: methotrexate. Birth Defects Res A Clin Mol Teratol. 2012;94:187–207.

    Article  CAS  PubMed  Google Scholar 

  12. Shaw GM, Wasserman CR, Lammer EJ, O’Malley CD, Murray JC, Basart AM, Tolarova MM. Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants. Am J Hum Genet. 1996;58:551–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Butali A, Little J, Chevrier C, Cordier S, Steegers-Theunissen R, Jugessur A, Oladugba B, Mossey PA. Folic acid supplementation use and the MTHFR C677T polymorphism in orofacial clefts etiology: an individual participant data pooled-analysis. Birth Defects Res A Clin Mol Teratol. 2013;97:509–14.

    Article  CAS  PubMed  Google Scholar 

  14. Fraser FC, Sajoo A. Teratogenic potential of corticosteroids in humans. Teratology. 1995;51:45–6.

    Article  CAS  PubMed  Google Scholar 

  15. Grosen D, Chevrier C, Skytthe A, Bille C, Mølsted K, Sivertsen A, Murray JC, Christensen K. A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance. J Med Genet. 2010;47:162–8.

    Google Scholar 

  16. Rasmussen SA, Wong LYC, Yang Q, May KM, Friedman JM. Population-based analyses of mortality in trisomy 13 and trisomy 18. Pediatrics. 2003;111:777–84.

    Article  PubMed  Google Scholar 

  17. Zollino M, Murdolo M, Marang G, Pecile V, Galasso C, Mazzanti L, Neri G. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet. 2008;148C:257–69.

    Article  CAS  PubMed  Google Scholar 

  18. De Vries BB, Knight SJ, Homfray T, Smithson SF, Flint J, Winter RM. Submicroscopic subtelomeric 1qter deletions: a recognisable phenotype? J Med Genet. 2001;38:175–8.

    Article  PubMed  Google Scholar 

  19. Digilio MC, Bernardini L, Mingarell R, Capolino R, Capalbo A, Giuffrida MG, Versacci P, Novelli A, Dallapiccola B. 3q29 Microdeletion: a mental retardation disorder unassociated with a recognizable phenotype in two mother-daughter pairs. Am J Med Genet A. 2009;149A:1777–81.

    Article  CAS  PubMed  Google Scholar 

  20. Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, de Lima RLF, Daack-Hirsch S, Sander A, et al. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet. 2002;32:285–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJ, Stephens K, Robin NH, Moran RT, et al. Stickler syndrome. Seattle: University of Washington, Seattle; 1993.

    Google Scholar 

  22. Saka D, Trainor PA. Treacher Collins syndrome: unmasking the role of Tcof1/treacle. Int J Biochem Cell Biol. 2009;41:1229–32.

    Article  Google Scholar 

  23. Cole P, Hatef DA, Kaufman Y, Magruder A, Bree A, Friedman E, Sindwani R, Hollier LH. Facial clefting and oroauditory pathway manifestations in ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. Am J Med Genet A. 2009;149A:1910–5.

    Article  PubMed  Google Scholar 

  24. Nowaczyk MJM, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet. 2012;160C:250–62.

    Article  PubMed  Google Scholar 

  25. Arora K, Thukral A, Das RR, Gupta N, Kabra M, Agarwal R. Fryns syndrome: a lethal birth defect with variable phenotypic expressions in siblings. Indian J Pediatr. 2014;81:614–6.

    Article  PubMed  Google Scholar 

  26. Hu CH, Liu YF, Yu JS, Ng YY, Chen SJ, Su PH, Chen JY. A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain. Am J Med Genet A. 2012;158A:726–31.

    Article  PubMed  Google Scholar 

  27. Bisschoff IJ, Zeschnigk C, Horn D, Wellek B, Rieß A, Wessels M, Willems P, Jensen P, Busche A, Bekkebraten J, et al. Novel mutations including deletions of the entire OFD1 gene in 30 families with type 1 orofaciodigital syndrome: a study of the extensive clinical variability. Hum Mutat. 2013;34:237–47.

    Article  CAS  PubMed  Google Scholar 

  28. Tessier P. Anatomical classification facial, cranio-facial and latero-facial clefts. J Maxillofac Surg. 1976;4:69–92.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Human Genetics, Prenatal genetic diagnosis service, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Arie Koifman MD

  2. Department of Diagnostic Imaging, Division of Paediatric Neuroradiology; Department of Pediatrics, Division of Paediatric Neuroradiology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Susan Blaser MD (Professor of Medical Imaging (Neuroradiology)

  3. Department of Obstetrics and Gynecology, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, The Ontario Power Generation Building, 700 University Avenue, Room 3-709, Toronto, ON, M5G 1Z5, Canada

    David Chitayat MD, FABMG, FACMG, FCCMG, FRCPC

  4. Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    David Chitayat MD, FABMG, FACMG, FCCMG, FRCPC

Authors
  1. Arie Koifman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan Blaser MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Chitayat MD, FABMG, FACMG, FCCMG, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Chitayat MD, FABMG, FACMG, FCCMG, FRCPC .

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, Prenatal Diagnostic Service, Guastalla Civil Hospital AUSL Reggio Emilia, Reggio Emilia, Italy

    Gabriele Tonni

  2. Maternal-Fetal Diagnostic Center, Fetalmed, Santiago, Chile

    Waldo Sepulveda

  3. Department of Maternal-Fetal Medicine Palo Alto Medical Foundation, Mountain View, California, USA

    Amy E. Wong

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Koifman, A., Blaser, S., Chitayat, D. (2017). The Genetics of Facial Cleft. In: Tonni, G., Sepulveda, W., Wong, A. (eds) Prenatal Diagnosis of Orofacial Malformations. Springer, Cham. https://doi.org/10.1007/978-3-319-32516-3_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-32516-3_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-32514-9

  • Online ISBN: 978-3-319-32516-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation