Skip to main content
SpringerLink
Log in

Early Clinical Investigations and Management of Syndromes Affecting Craniofacial and Dental Structures

  • Chapter
  • First Online:
Fundamentals of Craniofacial Malformations

  • 1074 Accesses

Abstract

Syndromes affecting craniofacial and dental structures account for one-third of the congenital anomalies. Early diagnosis and treatment guided by an interdisciplinary team are of vital importance not only for an optimal outcome but also because these syndromes are associated often with life-threatening conditions. However, the affected craniofacial structures isolated or as part of a syndrome might not be identified early, especially in patients with unknown family history. Many craniofacial malformations and cognitive phenotypes are apparent only after the first years of life.

Moreover, the treatment of these patients is often complicated due to a lack of treatment guidelines and adequate medical knowledge. The role of the team is essential for the prevention, early diagnosis, and guidance for proper function and craniofacial development. Consideration of the patient’s developmental variations, deep phenotyping, and long-term clinical evaluation will assist in unraveling the phenotype-genotype correlations and further in an early diagnosis.

Despite knowledge gaps and lack of consensus in terminology and diagnostic criteria, this chapter aims to provide an update on the pathogenesis, general phenotypes, and oral and craniofacial manifestations for early diagnosis and clinical management. Furthermore, its goal is to promote interaction of the interdisciplinary team for a customized, intergraded, long-term treatment planning of these patients.

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

Access this chapter

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 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
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

Institutional subscriptions

References

  1. Sakai D, Dixon J, Achilleos A, Dixon M, Trainor PA. Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation. Nat Commun. 2016;7:10328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Best KE, Rankin J, Dolk H, Loane M, Haeusler M, Nelen V, et al. Multilevel analyses of related public health indicators: the European Surveillance of Congenital Anomalies (EUROCAT) public health indicators. Paediatr Perinat Epidemiol. 2020;34(2):122–9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dissemond J, Haberer D, Franckson T, Hillen U. The Van der Woude syndrome: a case report and review of the literature. J Eur Acad Dermatol Venereol. 2004;18(5):611–3.

    Article  CAS  PubMed  Google Scholar 

  4. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374(9703):1773–85.

    Article  PubMed  Google Scholar 

  5. Grosen D, Chevrier C, Skytthe A, Bille C, Molsted K, Sivertsen A, et al. 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(3):162–8.

    Article  PubMed  Google Scholar 

  6. Maili L, Letra A, Silva R, Buchanan EP, Mulliken JB, Greives MR, et al. PBX-WNT-P63-IRF6 pathway in nonsyndromic cleft lip and palate. Birth Defects Res. 2020;112(3):234–44.

    Google Scholar 

  7. Bartzela T. Treatment outcome in patients with bilateral cleft lip and palate. Nijmegen, The Netherlands: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 2011.

    Google Scholar 

  8. Leslie EJ, Koboldt DC, Kang CJ, Ma L, Hecht JT, Wehby GL, et al. IRF6 mutation screening in non-syndromic orofacial clefting: analysis of 1521 families. Clin Genet. 2016;90(1):28–34.

    Article  CAS  PubMed  Google Scholar 

  9. Khandelwal KD, Ishorst N, Zhou H, Ludwig KU, Venselaar H, Gilissen C, et al. Novel IRF6 mutations detected in orofacial cleft patients by targeted massively parallel sequencing. J Dent Res. 2017;96(2):179–85.

    Article  CAS  PubMed  Google Scholar 

  10. Mangold E, Reutter H, Birnbaum S, Walier M, Mattheisen M, Henschke H, et al. Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin. Am J Med Genet A. 2009;149a(12):2680–94.

    Article  PubMed  Google Scholar 

  11. Stanier P, Moore GE. Genetics of cleft lip and palate: syndromic genes contribute to the incidence of non-syndromic clefts. Hum Mol Genet. 2004;13. Spec No 1:R73–81.

    Article  CAS  PubMed  Google Scholar 

  12. Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet. 2002;61(4):248–56.

    Article  CAS  PubMed  Google Scholar 

  13. Shprintzen RJ, Siegel-Sadewitz VL, Amato J, Goldberg RB. Retrospective diagnoses of previously missed syndromic disorders among 1,000 patients with cleft lip, cleft palate, or both. Birth Defects Orig Artic Ser. 1985;21(2):85–92.

    CAS  PubMed  Google Scholar 

  14. Bartzela T, Katsaros C, Ronning E, Rizell S, Semb G, Bronkhorst E, et al. A longitudinal three-center study of craniofacial morphology at 6 and 12 years of age in patients with complete bilateral cleft lip and palate. Clin Oral Investig. 2012;16(4):1313–24.

    Article  PubMed  Google Scholar 

  15. McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015;1:15071.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Shprintzen RJ, Goldberg RB, Lewin ML, Sidoti EJ, Berkman MD, Argamaso RV, et al. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. 1978;15(1):56–62.

    CAS  PubMed  Google Scholar 

  17. Shprintzen RJ, Goldberg RB, Young D, Wolford L. The velo-cardio-facial syndrome: a clinical and genetic analysis. Pediatrics. 1981;67(2):167–72.

    Article  CAS  PubMed  Google Scholar 

  18. Bassett AS, Hodgkinson K, Chow EW, Correia S, Scutt LE, Weksberg R. 22q11 deletion syndrome in adults with schizophrenia. Am J Med Genet. 1998;81(4):328–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Campbell IM, Sheppard SE, Crowley TB, McGinn DE, Bailey A, McGinn MJ, et al. What is new with 22q? An update from the 22q and you Center at the Children's Hospital of Philadelphia. Am J Med Genet A. 2018;176(10):2058–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Morrow BE, McDonald-McGinn DM, Emanuel BS, Vermeesch JR, Scambler PJ. Molecular genetics of 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(10):2070–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cohen JL, Crowley TB, McGinn DE, McDougall C, Unolt M, Lambert MP, et al. 22q and two: 22q11.2 deletion syndrome and coexisting conditions. Am J Med Genet A. 2018;176(10):2203–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhao Y, Diacou A, Johnston HR, Musfee FI, McDonald-McGinn DM, McGinn D, et al. Complete sequence of the 22q11.2 allele in 1,053 subjects with 22q11.2 deletion syndrome reveals modifiers of conotruncal heart defects. Am J Hum Genet. 2020;106(1):26–40.

    Article  CAS  PubMed  Google Scholar 

  23. Hopkins SE, Chadehumbe M, Blaine Crowley T, Zackai EH, Bilaniuk LT, McDonald-McGinn DM. Neurologic challenges in 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(10):2140–5.

    Article  PubMed  Google Scholar 

  24. Klingberg G, Dietz W, Oskarsdottir S, Odelius H, Gelander L, Noren JG. Morphological appearance and chemical composition of enamel in primary teeth from patients with 22q11 deletion syndrome. Eur J Oral Sci. 2005;113(4):303–11.

    Article  CAS  PubMed  Google Scholar 

  25. Fiksinski AM, Schneider M, Murphy CM, Armando M, Vicari S, Canyelles JM, et al. Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(10):2182–91.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schindewolf E, Khalek N, Johnson MP, Gebb J, Coleman B, Crowley TB, et al. Expanding the fetal phenotype: prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(8):1735–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34(10):798–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wu D, Chen Y, Xu C, Wang K, Wang H, Zheng F, et al. Characteristic face: a key indicator for direct diagnosis of 22q11.2 deletions in Chinese velocardiofacial syndrome patients. PLoS One. 2013;8(1):e54404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nugent N, McGillivary A, Earley MJ. 22q11 chromosome abnormalities and the cleft service. J Plast Reconstr Aesthet Surg. 2010;63(4):598–602.

    Article  CAS  PubMed  Google Scholar 

  30. Toka O, Karl M, Dittrich S, Holst S, Holst A. Dental aspects in patients with DiGeorge syndrome. Quintessence Int. 2010;41(7):551–6.

    PubMed  Google Scholar 

  31. Vieira TP, Monteiro FP, Sgardioli IC, Souza J, Fett-Conte AC, Monlleo IL, et al. Clinical features in patients with 22q11.2 deletion syndrome ascertained by palatal abnormalities. Cleft Palate Craniofac J. 2015;52(4):411–6.

    Article  PubMed  Google Scholar 

  32. Al-Hertani W, Hastings VA, McGowan-Jordan J, Hurteau J, Graham GE. Severe craniosynostosis in an infant with deletion 22q11.2 syndrome. Am J Med Genet A. 2013;161a(1):153–7.

    Article  CAS  PubMed  Google Scholar 

  33. McDonald-McGinn DM. 22q11.2 deletion syndrome: a tiny piece leading to a big picture. Am J Med Genet A. 2018;176(10):2055–7.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wang JL, Chen SJ, Chung MY, Niu DM, Lin CY, Hwang BT, et al. DiGeorge syndrome with microdeletion of chromosome 22q11.2: report of one case. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1997;38(5):385–9.

    CAS  PubMed  Google Scholar 

  35. Gaspar IM, Lourenco MT, Reis MI, Soares MA, Nogueira G, Ferreira F, et al. The deletions of 22q11--the Portuguese experience. Genet Couns. 1999;10(1):51–7.

    CAS  PubMed  Google Scholar 

  36. Wang K, Yang Y, Shen F, Tao J, Xu H, Portnof JE, et al. Utilization of three-dimensional computed tomography for craniofacial phenotypic analysis in children with velocardiofacial syndrome. J Craniofac Surg. 2009;20(6):2013–9.

    Article  PubMed  Google Scholar 

  37. Oberoi S, Vargervik K. Velocardiofacial syndrome with single central incisor. Am J Med Genet A. 2005;132A(2):194–7.

    Article  PubMed  Google Scholar 

  38. Oberoi S, Huynh L, Vargervik K. Velopharyngeal, speech and dental characteristics as diagnostic aids in 22q11.2 deletion syndrome. J Calif Dent Assoc. 2011;39(5):327–32.

    PubMed  Google Scholar 

  39. Lewyllie A, Roosenboom J, Indencleef K, Claes P, Swillen A, Devriendt K, et al. A comprehensive craniofacial study of 22q11.2 deletion syndrome. J Dent Res. 2017;22034517720630

    Google Scholar 

  40. Wong NS, Feng Z, Rappazzo C, Turk C, Randall C, Ongkasuwan J. Patterns of dysphagia and airway protection in infants with 22q11.2-Deletion syndrome. Laryngoscope. 2019;

    Google Scholar 

  41. Heliovaara A, Rantanen I, Arte S. Dental development and tooth agenesis in children with velocardiofacial syndrome. Int J Paediatr Dent. 2011;21(6):446–50.

    Article  PubMed  Google Scholar 

  42. Fukui N, Amano A, Akiyama S, Daikoku H, Wakisaka S, Morisaki I. Oral findings in DiGeorge syndrome: clinical features and histologic study of primary teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89(2):208–15.

    Article  CAS  PubMed  Google Scholar 

  43. Nordgarden H, Lima K, Skogedal N, Folling I, Storhaug K, Abrahamsen TG. Dental developmental disturbances in 50 individuals with the 22q11.2 deletion syndrome; relation to medical conditions? Acta Odontol Scand. 2012;70(3):194–201.

    Article  CAS  PubMed  Google Scholar 

  44. da Silva DG, Richieri-Costa A, de Assis Taveira LA. Tooth abnormalities and soft tissue changes in patients with velocardiofacial syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106(2):e46–51.

    Article  Google Scholar 

  45. Caton J, Luder HU, Zoupa M, Bradman M, Bluteau G, Tucker AS, et al. Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors. Dev Biol. 2009;328(2):493–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mitsiadis TA, Tucker AS, De Bari C, Cobourne MT, Rice DP. A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination. Dev Biol. 2008;320(1):39–48.

    Article  CAS  PubMed  Google Scholar 

  47. Bassett AS, DM MD-MG, Devriendt K, Digilio MC, Goldenberg P, Habel A, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332–9.e1

    Article  PubMed  PubMed Central  Google Scholar 

  48. Swillen A, Moss E, Duijff S. Neurodevelopmental outcome in 22q11.2 deletion syndrome and management. Am J Med Genet A. 2018;176(10):2160–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Vo OK, McNeill A, Vogt KS. The psychosocial impact of 22q11 deletion syndrome on patients and families: a systematic review. Am J Med Genet A. 2018;176(10):2215–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gangopadhyay N, Mendonca DA, Woo AS. Pierre robin sequence. Semin Plast Surg. 2012;26(2):76–82.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Butow KW, Hoogendijk CF, Zwahlen RA. Pierre Robin sequence: appearances and 25 years of experience with an innovative treatment protocol. J Pediatr Surg. 2009;44(11):2112–8.

    Article  PubMed  Google Scholar 

  52. Breugem CC, Evans KN, Poets CF, Suri S, Picard A, Filip C, et al. Best practices for the diagnosis and evaluation of infants with Robin sequence: a clinical consensus report. JAMA Pediatr. 2016;170(9):894–902.

    Article  PubMed  Google Scholar 

  53. Logjes RJH, Haasnoot M, Lemmers PMA, Nicolaije MFA, van den Boogaard MH, van der Molen AB M, et al. Mortality in Robin sequence: identification of risk factors. Eur J Pediatr. 2018;177(5):781–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Anderson IC, Sedaghat AR, McGinley BM, Redett RJ, Boss EF, Ishman SL. Prevalence and severity of obstructive sleep apnea and snoring in infants with Pierre Robin sequence. Cleft Palate Craniofac J. 2011;48(5):614–8.

    Article  PubMed  Google Scholar 

  55. Akiyama H, Chaboissier MC, Martin JF, Schedl A, de Crombrugghe B. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 2002;16(21):2813–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mori-Akiyama Y, Akiyama H, Rowitch DH, de Crombrugghe B. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc Natl Acad Sci U S A. 2003;100(16):9360–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Jakobsen LP, Ullmann R, Christensen SB, Jensen KE, Molsted K, Henriksen KF, et al. Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2. J Med Genet. 2007;44(6):381–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Yang Y, Yuan J, Yao X, Zhang R, Yang H, Zhao R, et al. BMPR1B mutation causes Pierre Robin sequence. Oncotarget. 2017;8(16):25864–71.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Xu JX, Kilpatrick N, Baker NL, Penington A, Farlie PG, Tan TY. Clinical and molecular characterisation of children with Pierre Robin sequence and additional anomalies. Mol Syndromol. 2016;7(6):322–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Cleary B, Loane M, Addor MC, Barisic I, de Walle HEK, Matias Dias C, et al. Methadone, Pierre Robin sequence and other congenital anomalies: case-control study. Arch Dis Child Fetal Neonatal Ed. 2019;

    Google Scholar 

  61. Gomez-Ospina N, Bernstein JA. Clinical, cytogenetic, and molecular outcomes in a series of 66 patients with Pierre Robin sequence and literature review: 22q11.2 deletion is less common than other chromosomal anomalies. Am J Med Genet A. 2016;170a(4):870–80.

    Article  PubMed  CAS  Google Scholar 

  62. Evans AK, Rahbar R, Rogers GF, Mulliken JB, Volk MS. Robin sequence: a retrospective review of 115 patients. Int J Pediatr Otorhinolaryngol. 2006;70(6):973–80.

    Article  PubMed  Google Scholar 

  63. Pruzansky S, Richmond JB. Growth of mandible in infants with micrognathia; clinical implications. AMA Am J Dis Child. 1954;88(1):29–42.

    CAS  PubMed  Google Scholar 

  64. Vegter F, Hage JJ, Mulder JW. Pierre Robin syndrome: mandibular growth during the first year of life. Ann Plast Surg. 1999;42(2):154–7.

    CAS  PubMed  Google Scholar 

  65. Zellner EG, Reid RR, Steinbacher DM. The Pierre Robin mandible is Hypoplastic and morphologically abnormal. J Craniofac Surg. 2017;28(8):1946–9.

    Article  PubMed  Google Scholar 

  66. Suri S, Ross RB, Tompson BD. Craniofacial morphology and adolescent facial growth in Pierre Robin sequence. Am J Orthod Dentofac Orthop. 2010;137(6):763–74.

    Article  Google Scholar 

  67. Ozawa TO, Lorenzoni DC, de Oliveira LG, da Silva Filho OG. Facial profile evaluation of isolated Pierre Robin sequence. Cleft Palate Craniofac J. 2012;49(5):546–52.

    Article  PubMed  Google Scholar 

  68. Daskalogiannakis J, Ross RB, Tompson BD. The mandibular catch-up growth controversy in Pierre Robin sequence. Am J Orthod Dentofac Orthop. 2001;120(3):280–5.

    Article  CAS  Google Scholar 

  69. Krimmel M, Kluba S, Breidt M, Bacher M, Dietz K, Buelthoff H, et al. Three-dimensional assessment of facial development in children with Pierre Robin sequence. J Craniofac Surg. 2009;20(6):2055–60.

    Article  PubMed  Google Scholar 

  70. Purnell CA, Janes LE, Klosowiak JL, Gosain AK. Mandibular catch-up growth in Pierre Robin sequence: a systematic review. Cleft Palate Craniofac J. 2019;56(2):168–76.

    Article  PubMed  Google Scholar 

  71. van Lieshout MJ, Joosten KF, Mathijssen IM, Koudstaal MJ, Hoeve HL, van der Schroeff MP, et al. Robin sequence: a European survey on current practice patterns. J Craniomaxillofac Surg. 2015;43(8):1626–31.

    Article  PubMed  Google Scholar 

  72. Rogers GF, Lim AA, Mulliken JB, Padwa BL. Effect of a syndromic diagnosis on mandibular size and sagittal position in Robin sequence. J Oral Maxillofac Surg. 2009;67(11):2323–31.

    Article  PubMed  Google Scholar 

  73. van Lieshout MJ, Joosten KF, Hoeve HL, Mathijssen IM, Koudstaal MJ, Wolvius EB. Unravelling Robin sequence: considerations of diagnosis and treatment. Laryngoscope. 2014;124(5):E203–9.

    PubMed  Google Scholar 

  74. Cote A, Fanous A, Almajed A, Lacroix Y. Pierre Robin sequence: review of diagnostic and treatment challenges. Int J Pediatr Otorhinolaryngol. 2015;79(4):451–64.

    Article  PubMed  Google Scholar 

  75. Hong P, Kearns D. Airway characteristics of infants with Pierre Robin sequence who undergo mandibular distraction osteogenesis. Ear Nose Throat J. 2015;94(8):E25–9.

    PubMed  Google Scholar 

  76. Renault F, Baudon JJ, Galliani E, Flores-Guevara R, Marlin S, Garabedian EN, et al. Facial, lingual, and pharyngeal electromyography in infants with Pierre Robin sequence. Muscle Nerve. 2011;43(6):866–71.

    Article  PubMed  Google Scholar 

  77. El Amm CA, Denny A. Hyoid bone abnormalities in Pierre Robin patients. J Craniofac Surg. 2008;19(1):259–63.

    Article  PubMed  Google Scholar 

  78. Mateo-Castillo JF, Pagin O, Marchi Carvalho IM, Olano-Dextre TL, Teixeira das Neves L. Novel dental phenotype in non-syndromic Pierre Robin sequence: a retrospective study. Arch Oral Biol. 2019;97:170–5.

    Article  PubMed  Google Scholar 

  79. Antonarakis GS, Suri S. Prevalence and patterns of permanent tooth agenesis in patients with nonsyndromic Pierre Robin sequence. Am J Orthod Dentofac Orthop. 2014;145(4):452–60.

    Article  Google Scholar 

  80. Ranta R. A review of tooth formation in children with cleft lip/palate. Am J Orthod Dentofac Orthop. 1986;90(1):11–8.

    Article  CAS  Google Scholar 

  81. Laitinen SH. Sizes of dental arches in children with the Pierre Robin syndrome and isolated cleft palate aged from 0.2 to six years. Scand J Plast Reconstr Surg Hand Surg. 1993;27(4):285–90.

    Article  CAS  PubMed  Google Scholar 

  82. Laitinen SH, Ranta R. Sizes of dental arches in young adult patients with Pierre Robin sequence and isolated cleft palate. Acta Odontol Scand. 1998;56(2):85–9.

    Article  CAS  PubMed  Google Scholar 

  83. Sher AE. Mechanisms of airway obstruction in Robin sequence: implications for treatment. Cleft Palate Craniofac J. 1992;29(3):224–31.

    Article  CAS  PubMed  Google Scholar 

  84. van Lieshout MJ, Joosten KF, Mathijssen IM, Koudstaal MJ, Wolvius EB, van der Schroeff MP. Non-surgical and surgical interventions for airway obstruction in children with Robin sequence. J Craniomaxillofac Surg. 2016;44(12):1871–9.

    Article  PubMed  Google Scholar 

  85. Buchenau W, Wenzel S, Bacher M, Muller-Hagedorn S, Arand J, Poets CF. Functional treatment of airway obstruction and feeding problems in infants with Robin sequence. Arch Dis Child Fetal Neonatal Ed. 2017;102(2):F142–f6.

    Article  PubMed  Google Scholar 

  86. Muller-Hagedorn S, Buchenau W, Arand J, Bacher M, Poets CF. Treatment of infants with syndromic Robin sequence with modified palatal plates: a minimally invasive treatment option. Head Face Med. 2017;13(1):4.

    Article  PubMed  PubMed Central  Google Scholar 

  87. van Lieshout MJS, Joosten KFM, Koudstaal MJ, van der Schroeff MP, Dulfer K, Mathijssen IMJ, et al. Management and outcomes of obstructive sleep apnea in children with Robin sequence, a cross-sectional study. Clin Oral Investig. 2017;21(6):1971–8.

    Article  PubMed  Google Scholar 

  88. Ehsan Z, Kurian C, Weaver KN, Pan BS, Huang G, Hossain MM, et al. Longitudinal sleep outcomes in neonates with Pierre Robin sequence treated conservatively. J Clin Sleep Med. 2019;15(3):477–82.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Meyers AB, Zei MG, Denny AD. Imaging neonates and children with Pierre Robin sequence before and after mandibular distraction osteogenesis: what the craniofacial surgeon wants to know. Pediatr Radiol. 2015;45(9):1392–402.

    Article  PubMed  Google Scholar 

  90. Ren XC, Gao ZW, Li YF, Liu Y, Ye B, Zhu SS. The effects of clinical factors on airway outcomes of mandibular distraction osteogenesis in children with Pierre Robin sequence. Int J Oral Maxillofac Surg. 2017;46(7):805–10.

    Article  CAS  PubMed  Google Scholar 

  91. Butow KW, Naidoo S, Zwahlen RA, Morkel JA. Pierre Robin sequence: subdivision, data, theories, and treatment - part 4: recommended management and treatment of Pierre Robin sequence and its application. Ann Maxillofac Surg. 2016;6(1):44–9.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Paliga JT, Tahiri Y, Silvestre J, Taylor JA. Screening for obstructive sleep apnea in children treated at a major craniofacial center. J Craniofac Surg. 2014;25(5):1762–5.

    Article  PubMed  Google Scholar 

  93. Buchenau W, Urschitz MS, Sautermeister J, Bacher M, Herberts T, Arand J, et al. A randomized clinical trial of a new orthodontic appliance to improve upper airway obstruction in infants with Pierre Robin sequence. J Pediatr. 2007;151(2):145–9.

    Article  PubMed  Google Scholar 

  94. van Nunen DPF, van den Boogaard MH, Breugem CC. Robin sequence: continuing heterogeneity in nomenclature and diagnosis. J Craniofac Surg. 2018;29(4):985–7.

    Article  PubMed  Google Scholar 

  95. MacLean JE. Understanding the Spectrum of treatment options for infants with Pierre Robin sequence and airway obstruction. J Clin Sleep Med. 2019;15(3):373–4.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Izumi K, Konczal LL, Mitchell AL, Jones MC. Underlying genetic diagnosis of Pierre Robin sequence: retrospective chart review at two children's hospitals and a systematic literature review. J Pediatr. 2012;160(4):645–50. e2

    Article  PubMed  Google Scholar 

  97. Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr. 1981;99(4):570–3.

    Article  CAS  PubMed  Google Scholar 

  98. Burke LW, Jones MC. Kabuki syndrome: underdiagnosed recognizable pattern in cleft palate patients. Cleft Palate Craniofac J. 1995;32(1):77–84.

    Article  CAS  PubMed  Google Scholar 

  99. Schwenty-Lara J, Nehl D, Borchers A. The histone methyltransferase KMT2D, mutated in kabuki syndrome patients, is required for neural crest cell formation and migration. Hum Mol Genet. 2020;29(2):305–19.

    Article  CAS  PubMed  Google Scholar 

  100. Margot H, Genevieve D, Gatinois V, Arveiler B, Moutton S, Touitou I, et al. Typical facial gestalt in X-linked kabuki syndrome. Am J Med Genet A. 2016;170(12):3363–4.

    Article  CAS  PubMed  Google Scholar 

  101. Van Laarhoven PM, Neitzel LR, Quintana AM, Geiger EA, Zackai EH, Clouthier DE, et al. Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Hum Mol Genet. 2015;24(15):4443–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, et al. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007;449(7163):689–94.

    Article  CAS  PubMed  Google Scholar 

  103. Adam MP, Banka S, Bjornsson HT, Bodamer O, Chudley AE, Harris J, et al. Kabuki syndrome: international consensus diagnostic criteria. J Med Genet. 2019;56(2):89–95.

    Article  PubMed  Google Scholar 

  104. Schrander-Stumpel CT, Spruyt L, Curfs LM, Defloor T, Schrander JJ. Kabuki syndrome: clinical data in 20 patients, literature review, and further guidelines for preventive management. Am J Med Genet A. 2005;132A(3):234–43.

    Article  PubMed  Google Scholar 

  105. Ruault V, Corsini C, Duflos C, Akouete S, Georgescu V, Abaji M, et al. Growth charts in Kabuki syndrome 1. Am J Med Genet A. 2020;182(3):446–53.

    Article  CAS  PubMed  Google Scholar 

  106. Haanpaa M, Schlecht H, Batra G, Clayton-Smith J, Douzgou S. Interrupted/bipartite clavicle as a diagnostic clue in Kabuki syndrome. Am J Med Genet A. 2017;173(4):1115–8.

    Article  PubMed  CAS  Google Scholar 

  107. Yoon JK, Ahn KJ, Kwon BS, Kim GB, Bae EJ, Noh CI, et al. The strong association of left-side heart anomalies with Kabuki syndrome. Korean J Pediatr. 2015;58(7):256–62.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Yuan SM. Congenital heart defects in Kabuki syndrome. Cardiol J. 2013;20(2):121–4.

    Article  PubMed  Google Scholar 

  109. Tekin M, Fitoz S, Arici S, Cetinkaya E, Incesulu A. Niikawa-Kuroki (Kabuki) syndrome with congenital sensorineural deafness: evidence for a wide spectrum of inner ear abnormalities. Int J Pediatr Otorhinolaryngol. 2006;70(5):885–9.

    Article  PubMed  Google Scholar 

  110. Kawame H, Hannibal MC, Hudgins L, Pagon RA. Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr. 1999;134(4):480–5.

    Article  CAS  PubMed  Google Scholar 

  111. Gole H, Chuk R, Coman D. Persistent hyperinsulinism in Kabuki syndrome 2: case report and literature review. Clin Pract. 2016;6(3):848.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Matsune K, Shimizu T, Tohma T, Asada Y, Ohashi H, Maeda T. Craniofacial and dental characteristics of Kabuki syndrome. Am J Med Genet. 2001;98(2):185–90.

    Article  CAS  PubMed  Google Scholar 

  113. Tuna EB, Marsan G, Gencay K, Seymen F. Craniofacial and dental characteristics of Kabuki syndrome: nine years cephalometric follow-up. J Clin Pediatr Dent. 2012;36(4):393–400.

    Article  PubMed  Google Scholar 

  114. do Prado Sobral S, Leite AF, Figueiredo PT, Ferrari I, Safatle HP, Cordoba MS, et al. Craniofacial and dental features in kabuki syndrome patients. Cleft Palate Craniofac J. 2013;50(4):440–7.

    Article  Google Scholar 

  115. Porntaveetus T, Abid MF, Theerapanon T, Srichomthong C, Ohazama A, Kawasaki K, et al. Expanding the oro-dental and mutational spectra of Kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs. Int J Biol Sci. 2018;14(4):381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Rachmiel A, Turgeman S, Emodi O, Aizenbud D, Shilo D. Management of severely atrophic maxilla in ectrodactyly ectodermal dysplasia-cleft syndrome. Plast Reconstr Surg Glob Open. 2018;6(2):e1678.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Silva-Andrade N, Lopez-Ortega K, Gallottini M. Orofacial features and medical profile of eight individuals with Kabuki syndrome. Med Oral Patol Oral Cir Bucal. 2019;24(5):e630–e5.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Teixeira CS, Silva CR, Honjo RS, Bertola DR, Albano LM, Kim CA. Dental evaluation of Kabuki syndrome patients. Cleft Palate Craniofac J. 2009;46(6):668–73.

    Article  PubMed  Google Scholar 

  119. Petzold D, Kratzsch E, Opitz C, Tinschert S. The Kabuki syndrome: four patients with oral abnormalities. Eur J Orthod. 2003;25(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  120. Rocha CT, Peixoto IT, Fernandes PM, Torres CP, de Queiroz AM. Dental findings in Kabuki make-up syndrome: a case report. Spec Care Dentist. 2008;28(2):53–7.

    Article  PubMed  Google Scholar 

  121. Santos CN, Cardoso M, Turrioni AP, Santo ASM, Paranhos LR. Talon cusp in the temporary dentition of a patient with Kabuki syndrome: case report with a two-year follow-up. Spec Care Dentist. 2019;39(6):624–30.

    Article  PubMed  Google Scholar 

  122. Cogulu D, Oncag O, Celen E, Ozkinay F. Kabuki syndrome with additional dental findings: a case report. J Dent Child (Chic). 2008;75(2):185–7.

    Google Scholar 

  123. Digilio MC, Gnazzo M, Lepri F, Dentici ML, Pisaneschi E, Baban A, et al. Congenital heart defects in molecularly proven kabuki syndrome patients. Am J Med Genet A. 2017;173(11):2912–22.

    Article  CAS  PubMed  Google Scholar 

  124. Kurahashi N, Miyake N, Mizuno S, Koshimizu E, Kurahashi H, Yamada K, et al. Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations. Brain and Development. 2017;39(8):672–7.

    Article  PubMed  Google Scholar 

  125. Margot H, Boursier G, Duflos C, Sanchez E, Amiel J, Andrau JC, et al. Immunopathological manifestations in kabuki syndrome: a registry study of 177 individuals. Genet Med. 2020;22(1):181–8.

    Article  PubMed  Google Scholar 

  126. Cudzilo D, Czochrowska E. Orthodontic treatment of a Kabuki syndrome patient. Cleft Palate Craniofac J. 2018;55(8):1175–80.

    Article  PubMed  Google Scholar 

  127. Tsai IC, McKnight K, McKinstry SU, Maynard AT, Tan PL, Golzio C, et al. Small molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki syndrome. Sci Rep. 2018;8(1):10779.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Rintala AE, Ranta R. Lower lip sinuses: I. Epidemiology, microforms and transverse sulci. Br J Plast Surg. 1981;34(1):26–30.

    Article  CAS  PubMed  Google Scholar 

  129. Van Der Woude A. Fistula labii inferioris congenita and its association with cleft lip and palate. Am J Hum Genet. 1954;6(2):244–56.

    Google Scholar 

  130. Schinzel A, Klausler M. The Van der Woude syndrome (dominantly inherited lip pits and clefts). J Med Genet. 1986;23(4):291–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Fakhouri WD, Rahimov F, Attanasio C, Kouwenhoven EN, Ferreira De Lima RL, Felix TM, et al. An etiologic regulatory mutation in IRF6 with loss- and gain-of-function effects. Hum Mol Genet. 2014;23(10):2711–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Chu EY, Tamasas B, Fong H, Foster BL, LaCourse MR, Tran AB, et al. Full spectrum of postnatal tooth phenotypes in a novel Irf6 cleft lip model. J Dent Res. 2016;95(11):1265–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Botti E, Spallone G, Moretti F, Marinari B, Pinetti V, Galanti S, et al. Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas. Proc Natl Acad Sci U S A. 2011;108(33):13710–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Reardon JB, Brustowicz KA, Marrinan EM, Mulliken JB, Padwa BL. Anatomic severity, midfacial growth, and speech outcomes in Van der Woude/popliteal pterygium syndromes compared to nonsyndromic cleft lip/palate. Cleft Palate Craniofac J. 2015;52(6):676–81.

    Article  PubMed  Google Scholar 

  135. Busche A, Hehr U, Sieg P, Gillessen-Kaesbach G. Van der Woude and popliteal pterygium syndromes: broad intrafamilial variability in a three generation family with mutation in IRF6. Am J Med Genet A. 2016;170(9):2404–7.

    Article  CAS  PubMed  Google Scholar 

  136. Peyrard-Janvid M, Leslie EJ, Kousa YA, Smith TL, Dunnwald M, Magnusson M, et al. Dominant mutations in GRHL3 cause Van der Woude syndrome and disrupt oral periderm development. Am J Hum Genet. 2014;94(1):23–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Azevedo CMS, Machado RA, Martelli-Junior H, Reis SRA, Persuhn DC, Coletta RD, et al. Exploring GRHL3 polymorphisms and SNP-SNP interactions in the risk of non-syndromic oral clefts in the Brazilian population. Oral Dis. 2020;26(1):145–51.

    Article  PubMed  Google Scholar 

  138. Nopoulos P, Berg S, Canady J, Richman L, Van Demark D, Andreasen NC. Structural brain abnormalities in adult males with clefts of the lip and/or palate. Genet Med. 2002;4(1):1–9.

    Article  PubMed  Google Scholar 

  139. Nopoulos P, Langbehn DR, Canady J, Magnotta V, Richman L. Abnormal brain structure in children with isolated clefts of the lip or palate. Arch Pediatr Adolesc Med. 2007;161(8):753–8.

    Article  PubMed  Google Scholar 

  140. Nopoulos P, Richman L, Andreasen N, Murray JC, Schutte B. Cognitive dysfunction in adults with Van der Woude syndrome. Genet Med. 2007;9(4):213–8.

    Article  PubMed  Google Scholar 

  141. 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(1):17–24.

    Article  PubMed  Google Scholar 

  142. Robbins A, Zarate YA, Hartzell LD. Combined tongue-palate fusion with alveolar bands in a patient with Pierre Robin sequence and Van der Woude syndrome. Cleft Palate Craniofac J. 2019;56(1):123–6.

    Article  PubMed  Google Scholar 

  143. Los E, Baines H, Guttmann-Bauman I. Concurrent Van der Woude syndrome and turner syndrome: a case report. SAGE Open Med Case Rep. 2017;5:2050313x16687916.

    PubMed  PubMed Central  Google Scholar 

  144. Onofre MA, Brosco HB, Taga R. Relationship between lower-lip fistulae and cleft lip and/or palate in Von der Woude syndrome. Cleft Palate Craniofac J. 1997;34(3):261–5.

    Article  CAS  PubMed  Google Scholar 

  145. Janku P, Robinow M, Kelly T, Bralley R, Baynes A, Edgerton MT. The van der Woude syndrome in a large kindred: variability, penetrance, genetic risks. Am J Med Genet. 1980;5(2):117–23.

    Article  CAS  PubMed  Google Scholar 

  146. Heliovaara A, Karhulahti R, Rautio J. Craniofacial morphology in children with van der Woude syndrome and isolated cleft palate. J Plast Surg Hand Surg. 2015;49(4):209–13.

    Article  PubMed  Google Scholar 

  147. Kane AA, Liao YF, Lo LJ, Huang CS, Huang LM, Chen YR, et al. A cephalometric study of facial growth in van der Woude syndrome. Cleft Palate Craniofac J. 2002;39(2):219–25.

    Article  PubMed  Google Scholar 

  148. Oberoi S, Vargervik K. Hypoplasia and hypodontia in Van der Woude syndrome. Cleft Palate Craniofac J. 2005;42(5):459–66.

    Article  PubMed  Google Scholar 

  149. Nagore E, Sanchez-Motilla JM, Febrer MI, Serrano G, Bonillo J, Aliaga A. Congenital lower lip pits (Van der Woude syndrome): presentation of 10 cases. Pediatr Dermatol. 1998;15(6):443–5.

    Article  CAS  PubMed  Google Scholar 

  150. Krauel L, Parri FJ, Munoz E, Sancho AM, Gean E, Morales L. Van der Woude syndrome and lower lip pits treatment. J Oral Maxillofac Surg. 2008;66(3):589–92.

    Article  PubMed  Google Scholar 

  151. Hoefele J, Wilhelm C, Schiesser M, Mack R, Heinrich U, Weber LT, et al. Expanding the mutation spectrum for Fraser syndrome: identification of a novel heterozygous deletion in FRAS1. Gene. 2013;520(2):194–7.

    Article  CAS  PubMed  Google Scholar 

  152. Lam AK, David DJ, Townsend GC, Anderson PJ. Van der Woude syndrome: dentofacial features and implications for clinical practice. Aust Dent J. 2010;55(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  153. Ranta R, Rintala A. Tooth anomalies associated with congenital sinuses of the lower lip and cleft lip/palate. Angle Orthod. 1982;52(3):212–21.

    CAS  PubMed  Google Scholar 

  154. Phan M, Conte F, Khandelwal KD, Ockeloen CW, Bartzela T, Kleefstra T, et al. Tooth agenesis and orofacial clefting: genetic brothers in arms? Hum Genet. 2016;135(12):1299–327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Nawa H, Oberoi S, Vargervik K. Taurodontism and Van der Woude syndrome. Is there an association? Angle Orthod. 2008;78(5):832–7.

    Article  PubMed  Google Scholar 

  156. Richardson S, Khandeparker RV. Management of lip Pits in Van der Woude syndrome: a clinical classification with difficulty index. J Oral Maxillofac Surg. 2016;74(9):1849.e1-.e10

    Article  PubMed  Google Scholar 

  157. Peralta-Mamani M, Terrero-Perez A, Dalben G, Rubira CMF, Honorio HM, Rubira-Bullen IF. Treatment of lower lip pits in Van der Woude syndrome: a systematic review. Int J Oral Maxillofac Surg. 2018;47(4):421–7.

    Article  CAS  PubMed  Google Scholar 

  158. Jones JL, Canady JW, Brookes JT, Wehby GL, L'Heureux J, Schutte BC, et al. Wound complications after cleft repair in children with Van der Woude syndrome. J Craniofac Surg. 2010;21(5):1350–3.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Rhea L, Canady FJ, Le M, Reeb T, Canady JW, Kacmarynski DSF, et al. Interferon regulatory factor 6 is required for proper wound healing in vivo. Dev Dyn. 2019;

    Google Scholar 

  160. Nobeyama Y, Nakagawa H. Silencing of interferon regulatory factor gene 6 in melanoma. PLoS One. 2017;12(9):e0184444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. de Freitas EM, Machado RA, de Moura SE, de Matos FR, Galvao HC, Miranda Soares PB, et al. Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer. Arch Oral Biol. 2019;99:9–14.

    Article  PubMed  CAS  Google Scholar 

  162. Alfi D, Lam D, Gateno J. Branchial arch syndromes. Atlas Oral Maxillofac Surg Clin North Am. 2014;22(2):167–73.

    Article  PubMed  Google Scholar 

  163. Fan X, Wang Y, Fan Y, Du H, Luo N, Zhang S, et al. TCOF1 pathogenic variants identified by whole-exome sequencing in Chinese Treacher Collins syndrome families and hearing rehabilitation effect. Orphanet J Rare Dis. 2019;14(1):178.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Akram A, McKnight MM, Bellardie H, Beale V, Evans RD. Craniofacial malformations and the orthodontist. Br Dent J. 2015;218(3):129–41.

    Article  CAS  PubMed  Google Scholar 

  165. Renkema RW, Caron C, Pauws E, Wolvius EB, Schipper JAM, Rooijers W, et al. Extracraniofacial anomalies in craniofacial microsomia: retrospective analysis of 991 patients. Int J Oral Maxillofac Surg. 2019;48(9):1169–76.

    Article  CAS  PubMed  Google Scholar 

  166. Kaya O, Pluijmers BI, Staal F, Ruff C, Padwa BL, Koudstaal MJ, et al. Describing the mandible in patients with craniofacial microsomia based on principal component analysis and thin plate spline video analysis. Int J Oral Maxillofac Surg. 2019;48(3):302–8.

    Article  CAS  PubMed  Google Scholar 

  167. Birgfeld C, Heike C. Craniofacial Microsomia. Clin Plast Surg. 2019;46(2):207–21.

    Article  PubMed  Google Scholar 

  168. Beleza-Meireles A, Hart R, Clayton-Smith J, Oliveira R, Reis CF, Venancio M, et al. Oculo-auriculo-vertebral spectrum: clinical and molecular analysis of 51 patients. Eur J Med Genet. 2015;58(9):455–65.

    Article  PubMed  Google Scholar 

  169. Tokura TA, Miyazaki A, Igarashi T, Dehari H, Kobayashi JI, Miki Y, et al. Quantitative evaluation of cephalometric radiographs of patients with hemifacial microsomia. Cleft Palate Craniofac J. 2019;56(6):711–9.

    Article  PubMed  Google Scholar 

  170. Vento AR, LaBrie RA, Mulliken JB. The O.M.E.N.S. classification of hemifacial microsomia. Cleft Palate Craniofac J. 1991;28(1):68–76. discussion 7

    Article  CAS  PubMed  Google Scholar 

  171. Luquetti DV, Speltz ML, Wallace ER, Siebold B, Collett BR, Drake AF, et al. Methods and challenges in a cohort study of infants and toddlers with craniofacial Microsomia: the Clock study. Cleft Palate Craniofac J. 2019;56(7):877–89.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Tuin J, Tahiri Y, Paliga JT, Taylor JA, Bartlett SP. Distinguishing Goldenhar syndrome from craniofacial Microsomia. J Craniofac Surg. 2015;26(6):1887–92.

    Article  PubMed  Google Scholar 

  173. Vendramini-Pittoli S, Kokitsu-Nakata NM. Oculoauriculovertebral spectrum: report of nine familial cases with evidence of autosomal dominant inheritance and review of the literature. Clin Dysmorphol. 2009;18(2):67–77.

    Article  PubMed  Google Scholar 

  174. Chen X, Xu F, Liu F, Aung ZM, Chen W, Han W, et al. Whole-exome sequencing for monozygotic twins discordant for hemifacial microsomia. J Craniomaxillofac Surg. 2018;46(5):802–7.

    Article  PubMed  Google Scholar 

  175. Ballesta-Martinez MJ, Lopez-Gonzalez V, Dulcet LA, Rodriguez-Santiago B, Garcia-Minaur S, Guillen-Navarro E. Autosomal dominant oculoauriculovertebral spectrum and 14q23.1 microduplication. Am J Med Genet A. 2013;161a(8):2030–5.

    Article  PubMed  CAS  Google Scholar 

  176. Horgan JE, Padwa BL, LaBrie RA, Mulliken JB. OMENS-plus: analysis of craniofacial and extracraniofacial anomalies in hemifacial microsomia. Cleft Palate Craniofac J. 1995;32(5):405–12.

    Article  CAS  PubMed  Google Scholar 

  177. Spineli-Silva S, Bispo LM, Gil-da-Silva-Lopes VL, Vieira TP. Distal deletion at 22q11.2 as differential diagnosis in craniofacial Microsomia: case report and literature review. Eur J Med Genet. 2018;61(5):262–8.

    Article  PubMed  Google Scholar 

  178. Berenguer M, Tingaud-Sequeira A, Colovati M, Melaragno MI, Bragagnolo S, Perez ABA, et al. A novel de novo mutation in MYT1, the unique OAVS gene identified so far. Eur J Hum Genet. 2017;25(9):1083–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Zhang YB, Hu J, Zhang J, Zhou X, Li X, Gu C, et al. Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia. Nat Commun. 2016;7:10605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Guida V, Sinibaldi L, Pagnoni M, Bernardini L, Loddo S, Margiotti K, et al. A de novo proximal 3q29 chromosome microduplication in a patient with oculo auriculo vertebral spectrum. Am J Med Genet A. 2015;167a(4):797–801.

    Article  PubMed  CAS  Google Scholar 

  181. Gorlin RJ, Cohen MM Jr, Hennekam RCM. Syndromes of the head and neck. 4th ed. Oxford: Oxford University Press; 2001.

    Google Scholar 

  182. Therapontos C, Erskine L, Gardner ER, Figg WD, Vargesson N. Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proc Natl Acad Sci U S A. 2009;106(21):8573–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Chen Q, Zhao Y, Shen G, Dai J. Etiology and pathogenesis of hemifacial microsomia. J Dent Res. 2018;97(12):1297–305.

    Article  CAS  PubMed  Google Scholar 

  184. Heike CL, Wallace E, Speltz ML, Siebold B, Werler MM, Hing AV, et al. Characterizing facial features in individuals with craniofacial microsomia: a systematic approach for clinical research. Birth Defects Res A Clin Mol Teratol. 2016;106(11):915–26.

    Article  CAS  PubMed  Google Scholar 

  185. Choi J, Park SW, Kwon GY, Kim SH, Hur JA, Baek SH, et al. Influence of congenital facial nerve palsy on craniofacial growth in craniofacial microsomia. J Plast Reconstr Aesthet Surg. 2014;67(11):1488–95.

    Article  PubMed  Google Scholar 

  186. Kane AA, Lo LJ, Christensen GE, Vannier MW, Marsh JL. Relationship between bone and muscles of mastication in hemifacial microsomia. Plast Reconstr Surg. 1997;99(4):990–7. discussion 8-9

    Article  CAS  PubMed  Google Scholar 

  187. Telich-Tarriba JE, Contreras-Molinar C, Orihuela-Rodriguez A, Lesta-Compagnucci L, Carrillo-Cordova JR, Cardenas-Mejia A. Bite force and electromyographic activity of the masseter muscle in children with hemifacial microsomia. J Plast Surg Hand Surg. 2019;53(5):316–9.

    Article  PubMed  Google Scholar 

  188. Wang J, Liu E, Du L, Hu M. Soft tissue damage in patients with hemifacial microsomia. J Craniofac Surg. 2019;30(8):2449–50.

    Article  PubMed  Google Scholar 

  189. Ongkosuwito EM, van Neck JW, Wattel E, van Adrichem LN, Kuijpers-Jagtman AM. Craniofacial morphology in unilateral hemifacial microsomia. Br J Oral Maxillofac Surg. 2013;51(8):902–7.

    Article  CAS  PubMed  Google Scholar 

  190. Shibazaki-Yorozuya R, Yamada A, Nagata S, Ueda K, Miller AJ, Maki K. Three-dimensional longitudinal changes in craniofacial growth in untreated hemifacial microsomia patients with cone-beam computed tomography. Am J Orthod Dentofac Orthop. 2014;145(5):579–94.

    Article  Google Scholar 

  191. Kim BC, Bertin H, Kim HJ, Kang SH, Mercier J, Perrin JP, et al. Structural comparison of hemifacial microsomia mandible in different age groups by three-dimensional skeletal unit analysis. J Craniomaxillofac Surg. 2018;46(11):1875–82.

    Article  PubMed  Google Scholar 

  192. Vargervik K, Ousterhout DK, Farias M. Factors affecting long-term results in hemifacial microsomia. Cleft Palate J. 1986;23(Suppl 1):53–68.

    PubMed  Google Scholar 

  193. Schaal SC, Ruff C, Pluijmers BI, Pauws E, Looman CWN, Koudstaal MJ, et al. Characterizing the skull base in craniofacial microsomia using principal component analysis. Int J Oral Maxillofac Surg. 2017;46(12):1656–63.

    Article  CAS  PubMed  Google Scholar 

  194. Xu X, Zhang ZY, Li BH, Tang XJ, Yin L, Liu W. Three-dimensional measurement of maxillary involvement in hemifacial microsomia in children. J Craniofac Surg. 2020;31:444.

    Article  PubMed  Google Scholar 

  195. Seow WK, Urban S, Vafaie N, Shusterman S. Morphometric analysis of the primary and permanent dentitions in hemifacial microsomia: a controlled study. J Dent Res. 1998;77(1):27–38.

    Article  CAS  PubMed  Google Scholar 

  196. Caron C, Pluijmers BI, Wolvius EB, Looman CWN, Bulstrode N, Evans RD, et al. Craniofacial and extracraniofacial anomalies in craniofacial microsomia: a multicenter study of 755 patients. J Craniomaxillofac Surg. 2017;45(8):1302–10.

    Article  PubMed  Google Scholar 

  197. Szpalski C, Vandegrift M, Patel PA, Appelboom G, Fisher M, Marcus J, et al. Unilateral craniofacial microsomia: unrecognized cause of pediatric obstructive sleep Apnea. J Craniofac Surg. 2015;26(4):1277–82.

    Article  PubMed  Google Scholar 

  198. Ongkosuwito EM, de Gijt P, Wattel E, Carels CE, Kuijpers-Jagtman AM. Dental development in hemifacial microsomia. J Dent Res. 2010;89(12):1368–72.

    Article  CAS  PubMed  Google Scholar 

  199. Maruko E, Hayes C, Evans CA, Padwa B, Mulliken JB. Hypodontia in hemifacial microsomia. Cleft Palate Craniofac J. 2001;38(1):15–9.

    Article  CAS  PubMed  Google Scholar 

  200. Elsten E, Caron C, Dunaway DJ, Padwa BL, Forrest C, Koudstaal MJ. Dental anomalies in craniofacial microsomia: a systematic review. Orthod Craniofac Res. 2020;23(1):16–26.

    Article  PubMed  Google Scholar 

  201. Chen EH, Reid RR, Chike-Obi C, Minugh-Purvis N, Whitaker LA, Puchala J, et al. Tongue dysmorphology in craniofacial microsomia. Plast Reconstr Surg. 2009;124(2):583–9.

    Article  CAS  PubMed  Google Scholar 

  202. Martinelli P, Maruotti GM, Agangi A, Mazzarelli LL, Bifulco G, Paladini D. Prenatal diagnosis of hemifacial microsomia and ipsilateral cerebellar hypoplasia in a fetus with oculoauriculovertebral spectrum. Ultrasound Obstet Gynecol. 2004;24(2):199–201.

    Article  CAS  PubMed  Google Scholar 

  203. Takahashi-Ichikawa N, Susami T, Nagahama K, Ohkubo K, Okayasu M, Uchino N, et al. Evaluation of mandibular hypoplasia in patients with hemifacial microsomia: a comparison between panoramic radiography and three-dimensional computed tomography. Cleft Palate Craniofac J. 2013;50(4):381–7.

    Article  PubMed  Google Scholar 

  204. Nardi C, De Falco L, Selvi V, Lorini C, Calistri L, Colagrande S. Role of cone-beam computed tomography with a large field of view in Goldenhar syndrome. Am J Orthod Dentofac Orthop. 2018;153(2):269–77.

    Article  Google Scholar 

  205. Cassi D, Magnifico M, Gandolfinini M, Kasa I, Mauro G, Di Blasio A. Early orthopaedic treatment of hemifacial microsomia. Case Rep Dent. 2017;2017:7318715.

    PubMed  PubMed Central  Google Scholar 

  206. Nouri M, Farzan A. Nonsurgical treatment of hemifacial microsomia: a case report. Iran Red Crescent Med J. 2015;17(11):e19920.

    Article  PubMed  PubMed Central  Google Scholar 

  207. Lu TC, Kang GC, Yao CF, Liou EJ, Ko EW, Chen ZC, et al. Simultaneous maxillo-mandibular distraction in early adolescence as a single treatment modality for durable correction of type II unilateral hemifacial microsomia: follow-up till completion of growth. J Craniomaxillofac Surg. 2016;44(9):1201–8.

    Article  PubMed  Google Scholar 

  208. Wang J, Yuan L, Liu J, Mao L, Xia L, Fang B. Hemifacial microsomia treated with a hybrid technique combining distraction osteogenesis and a mandible-guided functional appliance: pilot study. Am J Orthod Dentofac Orthop. 2019;155(6):801–11.

    Article  Google Scholar 

  209. Kaban LB, Padwa B, Mulliken JB. Mandibular deformity in hemifacial microsomia: a reassessment of the Pruzansky and Kaban classification. Plast Reconstr Surg. 2014;134(4):657e–8e.

    Article  CAS  PubMed  Google Scholar 

  210. Zhang J, Zhang W, Shen SG. Segmental maxillary distraction osteogenesis with a hybrid-type distractor in the management of wide alveolar cleft. Cleft Palate Craniofac J. 2018; 1055665618763329

    Google Scholar 

  211. Emodi O, Israel Y, Almos ME, Aizenbud D, Van Aalst JA, Rachmiel A. Three-dimensional planning and reconstruction of the mandible in children with craniofacial Microsomia type III using costochondral grafts. Ann Maxillofac Surg. 2017;7(1):64–72.

    PubMed  PubMed Central  Google Scholar 

  212. Liu Z, Cao J, Qian Y, Sun H, Sun Y, Shen SG, et al. Course of the mandibular canal in hemifacial microsomia: a retrospective computed tomography study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;128:558.

    Article  PubMed  Google Scholar 

  213. Zielinski D, Markus B, Sheikh M, Gymrek M, Chu C, Zaks M, et al. OTX2 duplication is implicated in hemifacial microsomia. PLoS One. 2014;9(5):e96788.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  214. Sato TS, Handa A, Priya S, Watal P, Becker RM, Sato Y. Neurocristopathies: enigmatic appearances of neural crest cell-derived abnormalities. Radiographics. 2019;39(7):2085–102.

    Article  PubMed  Google Scholar 

  215. Dixon J, Trainor P, Dixon MJ. Treacher Collins syndrome. Orthod Craniofac Res. 2007;10(2):88–95.

    Article  PubMed  Google Scholar 

  216. van Gijn DR, Tucker AS, Cobourne MT. Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome. Br J Oral Maxillofac Surg. 2013;51(5):384–8.

    Article  PubMed  Google Scholar 

  217. Hayano T, Yanagida M, Yamauchi Y, Shinkawa T, Isobe T, Takahashi N. Proteomic analysis of human Nop56p-associated pre-ribosomal ribonucleoprotein complexes. Possible link between Nop56p and the nucleolar protein treacle responsible for Treacher Collins syndrome. J Biol Chem. 2003;278(36):34309–19.

    Article  CAS  PubMed  Google Scholar 

  218. Posnick JC, Ruiz RL. Treacher Collins syndrome: current evaluation, treatment, and future directions. Cleft Palate Craniofac J. 2000;37(5):434.

    Article  CAS  PubMed  Google Scholar 

  219. Ribeiro AA, Smith FJ, Nary Filho H, Trindade IEK, Tonello C, Trindade-Suedam IK. Three-dimensional upper airway assessment in Treacher Collins syndrome. Cleft Palate Craniofac J. 2020;57(3):371–7.

    Article  PubMed  Google Scholar 

  220. Arvystas M, Shprintzen RJ. Craniofacial morphology in Treacher Collins syndrome. Cleft Palate Craniofac J. 1991;28(2):226–30. discussion 30-1

    Article  CAS  PubMed  Google Scholar 

  221. Vincent M, Genevieve D, Ostertag A, Marlin S, Lacombe D, Martin-Coignard D, et al. Treacher Collins syndrome: a clinical and molecular study based on a large series of patients. Genet Med. 2016;18(1):49–56.

    Article  PubMed  Google Scholar 

  222. Plomp RG, van Lieshout MJ, Joosten KF, Wolvius EB, van der Schroeff MP, Versnel SL, et al. Treacher Collins syndrome: a systematic review of evidence-based treatment and recommendations. Plast Reconstr Surg. 2016;137(1):191–204.

    Article  CAS  PubMed  Google Scholar 

  223. Martelli-Junior H, Coletta RD, Miranda RT, Barros LM, Swerts MS, Bonan PR. Orofacial features of Treacher Collins syndrome. Med Oral Patol Oral Cir Bucal. 2009;14(7):E344–8.

    PubMed  Google Scholar 

  224. da Silva DG, Costa B, Gomide MR. Prevalence of dental anomalies, ectopic eruption and associated oral malformations in subjects with Treacher Collins syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(5):588–92.

    Article  Google Scholar 

  225. Osterhus IN, Skogedal N, Akre H, Johnsen UL, Nordgarden H, Asten P. Salivary gland pathology as a new finding in Treacher Collins syndrome. Am J Med Genet A. 2012;158a(6):1320–5.

    Article  PubMed  CAS  Google Scholar 

  226. Ghesh L, Vincent M, Delemazure AS, Boyer J, Corre P, Perez F, et al. Autosomal recessive Treacher Collins syndrome due to POLR1C mutations: report of a new family and review of the literature. Am J Med Genet A. 2019;179(7):1390–4.

    PubMed  Google Scholar 

  227. Choi YS, Lee YH, Kim YD. Bilateral parotid gland agenesis in Treacher Collins syndrome: a case report. Ear Nose Throat J. 2019;98(10):625–6.

    Article  PubMed  Google Scholar 

  228. Thompson JT, Anderson PJ, David DJ. Treacher Collins syndrome: protocol management from birth to maturity. J Craniofac Surg. 2009;20(6):2028–35.

    Article  PubMed  Google Scholar 

  229. Travieso R, Chang CC, Terner JS, Beckett J, Wong K, Teng E, et al. A range of condylar hypoplasia exists in Treacher Collins syndrome. J Oral Maxillofac Surg. 2013;71(2):393–7.

    Article  PubMed  Google Scholar 

  230. Bradley D, Willson T, Chang JB, Gandolfi B, Zhu TR, Bradley JP, et al. Intraoperative three-dimensional virtual reality and computed tomographic guidance in temporomandibular joint arthroplasty of syndromic craniofacial Dysostoses. Plast Reconstr Surg Glob Open. 2019;7(9):e2388.

    PubMed  PubMed Central  Google Scholar 

  231. Plomp RG, Mathijssen IM, Moolenburgh SE, van Montfort KA, van der Meulen JJ, Poublon RM. Nasal sequelae of Treacher Collins syndrome. J Plast Reconstr Aesthet Surg. 2015;68(6):771–81.

    Article  PubMed  Google Scholar 

  232. Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med. 2008;14(2):125–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Rosas MG, Lorenzatti A, Porcel de Peralta MS, Calcaterra NB, Coux G. Proteasomal inhibition attenuates craniofacial malformations in a zebrafish model of Treacher Collins syndrome. Biochem Pharmacol. 2019;163:362–70.

    Article  CAS  PubMed  Google Scholar 

  234. Brons S, Darroudi A, Nada R, Bronkhorst EM, Vreeken R, Berge SJ, et al. Influence of involuntary facial expressions on reproducibility of 3D stereophotogrammetry in children with and without complete unilateral cleft lip and palate from 3 to 18 months of age. Clin Oral Investig. 2019;23(3):1041–50.

    Article  PubMed  Google Scholar 

  235. Richmond S, Howe LJ, Lewis S, Stergiakouli E, Zhurov A. Facial genetics: a brief overview. Front Genet. 2018;9:462.

    Article  PubMed  PubMed Central  Google Scholar 

  236. Bartzela TN, Carels C, Maltha JC. Update on 13 syndromes affecting craniofacial and dental structures. Front Physiol. 2017;8:1038.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthodontics, Dentofacial Orthopedics and Pedodontics, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center 3 (CC3) of Dental and Craniofacial Sciences, Berlin, Germany

    Theodosia Bartzela

Authors
  1. Theodosia Bartzela
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Theodosia Bartzela .

Editor information

Editors and Affiliations

  1. Craniofacial Center, Kieferklinik Münster, Münster, Germany

    Ulrich Meyer

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bartzela, T. (2021). Early Clinical Investigations and Management of Syndromes Affecting Craniofacial and Dental Structures. In: Meyer, U. (eds) Fundamentals of Craniofacial Malformations. Springer, Cham. https://doi.org/10.1007/978-3-030-46024-2_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-46024-2_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-46023-5

  • Online ISBN: 978-3-030-46024-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation