Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 5, September-October, p. 977–987

doi: 10.17219/acem/61911

Publication type: review

Language: English

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Genetic Factors in Selected Complex Congenital Malformations with Cleft Defect

Piotr Wójcicki1,A,D,E,F, Maciej J. Koźlik1,B,C,D, Karolina Wójcicka2,B,C,D

1 Department of Plastic Surgery, Wroclaw Medical University, Polanica-Zdrój, Poland

2 Department of Plastic Surgery, Specialist Medical Center, Polanica-Zdrój, Poland

Abstract

Cleft lips, alveolar ridges and palates are among the most common birth defects. There are over 500 different complex genetic disorders that include cleft defects. The most common related defects include abnormalities of the skeleton, skull, cardiovascular and nervous system. The occurrence of a cleft results from the interplay of multiple genes and environmental factors. Several thousand different mutations responsible for these syndromes have been discovered, whereas there are still numerous phenotypic cases of unknown genetic origin. The aim of this study was to present various clinical aspects and the latest discoveries with regard to genetic research in complex malformations, such as Van der Woude syndrome, popliteal pterygium syndrome, EEC syndrome, Pierre Robin sequence, various forms of Stickler syndrome, and Treacher Collins syndrome. These complex syndromes have different incidences, and most of them also have allelic variants with characteristic severities that differ even among close relatives. Easier access to genetic counseling and the lower cost of DNA testing in recent years can lead to new findings on the causes of such syndromes.

Key words

Treacher Collins syndrome, cleft palate, cleft lip, Pierre Robin syndrome, Van der Woude syndrome

References (62)

  1. Bender PL: Genetics of cleft lip and palate. J Pediatr Nurs 2000, 15, 242–249.
  2. Murray JC: Gene/environment causes of cleft lip and/or palate. Clin Genet 2002, 61, 248–256.
  3. Dixon MJ, Marazita ML, Beaty TH: Cleft lip and palate: Understanding genetic and environmental influences. Nat Rev Genet 2011, 12, 167–178.
  4. Fitzpatrick D, Farrall M: An estimation of the number of susceptibility loci for isolated cleft palate. J Craniofac Genet Dev Biol 1993, 13, 230–235.
  5. Boo-Chai K. An ancient Chinese text on a cleft lip. Plast Reconstr Surg 1966, 38, 89–91.
  6. Von Graefe CF: Bericht über die erste Staphyloplastick. Hufeland’s J 1817, 44, 116.
  7. Von Langenbeck G: Operation der angeborenen totalen Spaltung des harten Gaumens nach einer neuen Methode. Deutsche Klin 1861, 8, 231–232.
  8. Veau, V: La division palatine. Paris: Masson 1931.
  9. Johnson CY, Little J: Folate intake, markers of folate status and oral clefts: Is the evidence converging? Int J Epidemiol 2008, 37, 1041–1058.
  10. Johansen AM, Lie RT, Wilcox AJ: Maternal dietary intake of vitamin A and risk of orofacial clefts: A populationbased case-control study in Norway. Am J Epidemiol 2008, 167, 1164–1170.
  11. McKinney CM, Chowchuen B, Pitiphat W: Micronutrients and oral clefts: A case-control study. J Dent Res 2013, 92, 1089–1094.
  12. Wang W, Guan P, Xu W: Risk factors for oral clefts: A population-based case-control study in Shenyang, China. Paediatr Perinat Epidemiol 2009, 23, 310–320.
  13. Van der Woude A: Fistula labii inferioris congenita and its association with cleft lip and palate. Am J Hum Genet 1954, 6, 244–256.
  14. Rizos M, Spyropoulos MN: Van der Woude syndrome: A review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counselling and treatment. Eur J Orthod 2004, 26, 17–24.
  15. Wójcicki P, Kobus K, Wójcicka K: Van der Woude syndrome. Dent Med Probl 2007, 44, 18–21.
  16. Mostowska A, Wójcicki P, Kobus K: Gene symbol: IRF6. Disease: Van der Woude syndrome. Hum Genet 2005, 116, 534.
  17. Kondo S, Schutte BC, Richardson RJ: Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 2002, 32, 285–289.
  18. Leslie EJ, Standley J, Compton J: Comparative analysis of IRF6 variants in families with Van der Woude syndrome and popliteal pterygium syndrome using public whole-exome databases. Genet Med 2013, 15, 338–344.
  19. Peyrard-Janvid M, Leslie EJ, Kousa YA: Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development. Am J Hum Genet 2014, 94, 23–32.
  20. Qasim M, Shaukat M: Popliteal pterygium syndrome: A rare entity. APSP J Case Rep 2012, 3, 5.
  21. Rüdiger RA, Haase W, Passarge E: Association of ectrodactyly, ectodermal dysplasia, and cleft lip-palate. Am J Dis Child 1970, 120, 160–163.
  22. Rosenberg JB, Butrus S, Bazemore MG: Ectrodactyly-ectodermal dysplasia-clefting syndrome causing blindness in a child. J AAPOS 2011, 15, 80–82.
  23. Trope BM, Salomão JN, Costa VD: Do you know this syndrome? Ectrodactyly – ectodermal dysplasia – cleft lip/ palate (EEC) syndrome. An Bras Dermatol 2010, 85, 573–575.
  24. Wójcicki P, Wysocki M, Wójcicka K: Ectrodactyly-ectodermal dysplasia-clefting syndrome-plastic surgeon’s considerations. J Craniofac Surg 2010, 21, 1388–1392.
  25. Rollnick BR, Hoo JJ: Genitourinary anomalies are a component manifestation in the ectodermal dysplasia, ectrodactyly, cleft lip/palate (EEC) syndrome. Am J Med Genet 1988, 29, 131–136.
  26. Marwaha M, Nanda KD: Ectrodactyly, ectodermal dysplasia, cleft lip, and palate (EEC syndrome). Contemp Clin Dent 2012, 3, 205–208.
  27. Shivaprakash PK, Joshi HV, Noorani H: Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome: A case report of “Incomplete syndrome”. Contemp Clin Dent 2012, 3, Suppl 1, 115–117.
  28. Barbaro V, Confalonieri L, Vallini I: Development of an allele-specific real-time PCR assay for discrimination and quantification of p63 R2 79H mutation in EEC syndrome. J Mol Diagn 2012, 14, 38–45.
  29. Kosaki R, Kaneko T, Torii C, Kosaki K: EEC syndrome-like phenotype in a patient with an IRF6 mutation. Am J Med Genet, Part A, 2012, 158A, 1219–1220.
  30. Breugem CC, Mink van der Molen AB: What is ‘Pierre Robin sequence’? J Plast Reconstr Aesthet Surg 2009, 62, 1555–1558.
  31. Sherer DM, Metlay LA, Woods JR Jr: Lack of mandibular movement manifested by absent fetal swallowing: A possible factor in the pathogenesis of micrognathia. Am J Perinatol 1995 12, 30–33.
  32. Selvi R, Mukunda Priyanka A: Role of SOX9 in the etiology of Pierre-Robin Syndrome. Iran J Basic Med Sci 2013, 16, 700–704.
  33. Bridgewater LC, Lefebvre V, de Crombrugghe B: Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer. J Biol Chem 1998, 273, 14998–15006.
  34. Jakobsen LP, Ullmann R, Christensen SB: Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2. J Med Genet 2007, 44, 381–386.
  35. Rainger JK, Bhatia S, Bengani H: Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic form of Pierre Robin sequence. Hum Mol Genet 2014 23, 2569–2579.
  36. Stewart K, Uetani N, Hendriks W: Inactivation of LAR family phosphatase genes Ptprs and Ptprf causes craniofacial malformations resembling Pierre-Robin sequence. Development 2013, 140, 3413–3422.
  37. Stickler GB, Belau PG, Farrell FJ: Hereditary progressive arthro-ophthalmopathy. Mayo Clin Proc 1965, 40, 433–455.
  38. Hoornaert KP, Vereecke I, Dewinter C: Stickler syndrome caused by COL2A1 mutations: Genotype-phenotype correlation in a series of 100 patients. Eur J Hum Genet 2010, 18, 872–880.
  39. Snead MP, McNinch AM, Poulson AV: Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye (Lond) 2011, 25, 1389–1400.
  40. Ang A, Poulson AV, Goodburn SF: Retinal detachment and prophylaxis in type 1 Stickler syndrome. Ophthalmology 2008, 115, 164–168.
  41. Parke DW: Stickler syndrome: Clinical care and molecular genetics. Am J Ophthalmol 2002, 134, 746–748.
  42. Zechi-Ceide RM, Jesus Oliveira NA, Guion-Almeida ML: Clinical evaluation and COL2A1 gene analysis in 21 Brazilian families with Stickler syndrome: Identification of novel mutations, further genotype/phenotype correlation, and its implications for the diagnosis. Eur J Med Genet 2008, 51, 183–196.
  43. Poulson AV, Hooymans JM, Richards AJ: Clinical features of type 2 Stickler syndrome. J Med Genet 2004, 41, e107.
  44. Vijzelaar R, Waller S, Errami A: Deletions within COL11A1 in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA). BMC Med Genet 2013, 14, 48.
  45. Van Beelen E, Leijendeckers JM, Huygen PL: Audiometric characteristics of two Dutch families with non-ocular Stickler syndrome (COL11A2). Hear Res 2012, 291, 15–23.
  46. Van Camp G, Snoeckx RL, Hilgert N: A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet 2006, 79, 449–457.
  47. Nikopoulos K, Schrauwen I, Simon M: Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene. Invest Ophthalmol Vis Sci 2011, 52, 4774–4779.
  48. Faletra F, D’Adamo AP, Bruno I: Autosomal recessive Stickler syndrome due to a loss of function mutation in the COL9A3 gene. Am J Med Genet A 2014, 164A, 42–47.
  49. Richards AJ, Martin S, Yates JR: COL2A1 exon 2 mutations: Relevance to the Stickler and Wagner syndromes. Br J Ophthalmol 2000, 84, 364–371.
  50. Treacher Collis E: Cases with symmetrical congenital notches in the outer part of each lid and defective development of the malar bones. Trans Ophthalmol Soc UK 1900, 20, 190–192.
  51. Franceschetti A, Klein D: Mandibulo-facial dysostosis: New hereditary syndrome. Acta Ophtalmol 1949, 27, 143–224.
  52. Tessier P: Anatomical classification facial, cranio-facial and latero-facial clefts. J Maxillofac Surg 1976, 4, 69–92.
  53. Chang CC, Steinbacher DM: Treacher Collins syndrome. Semin Plast Surg 2012, 26, 83–90.
  54. Kobus K, Wójcicki P: Surgical treatment of Treacher Collins syndrome. Ann Plast Surg 2006, 56, 549–554.
  55. Wójcicki P, Marszałek-Kruk B: Uwarunkowania genetyczne oraz zasady leczenia zespołu Treachera Collinsa. Dent Med Probl 2005, 42, 619–626.
  56. Kadakia S, Helman SN, Badhey AK: Treacher Collins Syndrome: The genetics of a craniofacial disease. Int J Pediatr Otorhinolaryngol 2014, 78, 893–898.
  57. Marszałek-Kruk BA, Wójcicki P, Śmigiel R: Novel insertion in exon 5 of the TCOF1 gene in twin sisters with Treacher Collins syndrome. J Appl Genet 2012, 53, 279–282.
  58. Sloan KE, Bohnsack MT, Watkins NJ: The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress. Cell Rep 2013, 5, 237–247.
  59. Weiner AM, Scampoli NL, Calcaterra NB: Fishing the molecular bases of Treacher Collins syndrome. PLoS One 2012, 7, e29574.
  60. Bowman M, Oldridge M, Archer C: Gross deletions in TCOF1 are a cause of Treacher-Collins-Franceschetti syndrome. Eur J Hum Genet 2012, 20, 769–777.
  61. Dauwerse JG, Dixon J, Seland S: Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet 2011, 43, 20–22.
  62. Schaefer E, Collet C, Genevieve D: Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. Genet Med 2014, 16, 720–724.
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