Key Points
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Describes epidemiological features associated with human supernumerary teeth.
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Classifies human supernumerary teeth according to morphology.
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Outlines molecular signalling pathways implicated in controlling tooth number in mouse models.
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Discusses the relevance of these molecules in relation to human supernumerary teeth occuring in isolation or as part of identified syndromes.
Abstract
Supernumerary teeth are a common clinical and radiographic finding and may produce occlusal and dental problems. The aetiological basis of extra teeth is poorly understood in human populations; however, the mouse provides a useful model system to investigate the complex genetics of tooth development. This article describes recent advances in our understanding of the genetic basis of supernumerary teeth. We have reviewed biological evidence that provides insight into why supernumerary tooth formation may occur. Indeed, many of the molecular signalling pathways known to be involved in normal development of the tooth germ can also give rise to additional teeth if inappropriately regulated. These include components of the Hedgehog, FGF, Wnt, TNF and BMP families, which provide a useful resource of candidate genes that may potentially play a role in human supernumerary tooth formation.
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References
Schulze C. Developmental abnormalities of the teeth and jaws. In Gorlin R J, Goldman H M (eds). Thoma's oral pathology, 6th ed. pp 96–183. St Louis, USA: Mosby Company, 1970.
Backman B, Wahlin Y B . Variations in number and morphology of permanent teeth in 7-year-old Swedish children. Int J Paediatr Dent 2001; 11: 11–17.
Yusof W Z. Non-syndrome multiple supernumerary teeth: literature review. J Can Dent Assoc 1990; 56: 147–149.
Rajab L D, Hamdan M A . Supernumerary teeth: review of the literature and a survey of 152 cases. Int J Paediatr Dent 2002; 12: 244–254.
Garvey M T, Barry H J, Blake M . Supernumerary teeth - an overview of classification, diagnosis and management. J Can Dent Assoc 1999; 65: 612–616.
Brook A H. Dental anomalies of number, form and size: their prevalence in British schoolchildren. J Int Assoc Dent Child 1974; 5: 37–53.
Vichi M, Franchi L . Abnormalities of the maxillary incisors in children with cleft lip and palate. ASDC J Dent Child 1995; 62: 412–417.
Jensen B L, Kreiborg S . Development of the dentition in cleidocranial dysplasia. J Oral Pathol Med 1990; 19: 89–93.
Kreiborg S, Jensen B L, Larsen P et al. Anomalies of craniofacial skeleton and teeth in cleidocranial dysplasia. J Craniofac Genet Dev Biol 1999; 19: 75–79.
Fader M, Kline S N, Spatz S S et al. Gardner's syndrome (intestinal polyposis, osteomas, sebaceous cysts) and a new dental discovery. Oral Surg Oral Med Oral Pathol 1962; 15: 153–172.
Wolf J, Jarvinen H J, Hietanen J . Gardner's dento-maxillary stigmas in patients with familial adenomatosis coli. Br J Oral Maxillofac Surg 1986; 24: 410–416.
Kalra N, Chaudhary S, Sanghi S . Non-syndrome multiple supplemental supernumerary teeth. J Indian Soc Pedod Prev Dent 2005; 23: 46–48.
Orhan A I, Ozer L, Orhan K . Familial occurrence of nonsyndromal multiple supernumerary teeth. A rare condition. Angle Orthod 2006; 76: 891–897.
Primosch R E. Anterior supernumerary teeth - assessment and surgical intervention in children. Pediatr Dent 1981; 3: 204–215.
Di Biase D D. Midline supernumeraries and eruption of the maxillary central incisor. Dent Pract Dent Rec 1969; 20: 35–40.
Leyland L, Batra P, Wong F et al. A retrospective evaluation of the eruption of impacted permanent incisors after extraction of supernumerary teeth. J Clin Pediatr Dent 2006; 3 0: 225–231.
Mitchell L, Bennett T G . Supernumerary teeth causing delayed eruption-a retrospective study. Br J Orthod 1992; 19: 41–46.
Ashkenazi M, Greenberg B P, Chodik G et al. Postoperative prognosis of unerupted teeth after removal of supernumerary teeth or odontomas. Am J Orthod Dentofacial Orthop 2007; 131: 614–619.
Tucker A S, Sharpe P . The cutting edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 2004; 5: 499–508.
Cobourne M T. The genetic control of early odontogenesis. Br J Orthod 1999; 26: 21–28.
Jernvall J, Thesleff I . Reiterative signalling and patterning during mammalian tooth morphogenesis. Mech Dev 2000; 92: 19–29.
Berkovitz B K B, Holland G R, Moxham B J . Oral anatomy, embryology and histology. Edinburgh: Mosby International Ltd, 2002.
Tureckova J, Lesot H, Vonesch J L et al. Apoptosis is involved in the disappearance of the diastemal dental primordia in mouse embryo. Int J Dev Biol 1996; 40: 483–489.
Ferguson C A, Tucker A S, Sharpe P T. Temporospatial cell interactions regulating mandibular and maxillary arch patterning. Development 2000; 127: 403–412.
Cobourne M T, Hardcastle Z, Sharpe P T. Sonic hedgehog regulates epithelial proliferation and cell survival in the developing tooth germ. J Dent Res 2001; 80: 1974–1979.
Sarkar L, Cobourne M, Naylor S et al. Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proc Natl Acad Sci U S A 2000; 97: 4520–4524.
Cobourne M T, Miletich I, Sharpe P T. Restriction of sonic hedgehog signalling during early tooth development. Development 2004; 131: 2875–2885.
Zhang Q, Murcia N S, Chittenden L R et al. Loss of the Tg737 protein results in skeletal patterning defects. Dev Dyn 2003; 227: 78–90.
Ohazama A, Haycraft C J, Seppala M et al. Primary cilia regulate Shh activity in the control of molar tooth number. Development 2009; 136: 897–903.
Lee B, Thirunavukkarasu K, Zhou L et al. Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet 1997; 16: 307–310.
Mundlos S, Otto F, Mundlos C et al. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 1997; 89: 773–779.
D'Souza R N, Aberg T, Gaikwad J et al. Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development 1999; 126: 2911–2920.
Wang X P, Aberg T, James M J et al. Runx2 (Cbfa1) inhibits Shh signalling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth. J Dent Res 2005; 84: 138–143.
Jernvall J, Kettunen P, Karavanova I et al. Evidence for the role of the enamel knot as a control center in mammalian tooth cusp formation: non-dividing cells express growth stimulating Fgf-4 gene. Int J Dev Biol 1994; 38: 463–469.
Kettunen P, Karavanova I, Thesleff I . Responsiveness of developing dental tissues to fibroblast growth factors: expression of splicing alternatives of FGFR1,-2,-3, and of FGFR4; and stimulation of cell proliferation by FGF-2,-4,-8, and-9. Dev Genet 1998; 22: 374–385.
Kettunen P, Laurikkala J, Itaranta P et al. Associations of FGF-3 and FGF-10 with signalling networks regulating tooth morphogenesis. Dev Dyn 2000; 21 9: 322–332.
Kratochwil K, Galceran J, Tontsch S et al. FGF4, a direct target of LEF1 and Wnt signalling, can rescue the arrest of tooth organogenesis in Lef1(-/-) mice. Genes Dev 2002; 16: 3173–3185.
Mason J M, Morrison D J, Basson M A et al. Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signalling. Trends Cell Biol 2006; 16: 45–54.
Klein O D, Minowada G, Peterkova R et al. Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signalling. Dev Cell 2006; 11: 181–190.
Peterkova R, Churava S, Lesot H et al. Revitalization of a diastemal tooth primordium in Spry2 null mice results from increased proliferation and decreased apoptosis. J Exp Zool B Mol Dev Evol 2009; 312B: 292–308.
Kere J, Srivastava A K, Montonen O et al. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet 1996; 13: 409–416.
Thesleff I, Mikkola M L . Death receptor signalling giving life to ectodermal organs. Sci STKE 2002; 2002: pe22.
Monreal A W, Ferguson B M, Headon D J et al. Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia. Nat Genet 1999; 22: 366–369.
Mustonen T, Pispa J, Mikkola M L et al. Stimulation of ectodermal organ development by Ectodysplasin-A1. Dev Biol 2003; 259: 123–136.
Tucker A S, Headon D J, Courtney J M et al. The activation level of the TNF family receptor, Edar, determines cusp number and tooth number during tooth development. Dev Biol 2004; 268: 185–194.
Andl T, Reddy S T, Gaddapara T et al. WNT signals are required for the initiation of hair follicle development. Dev Cell 2002; 2: 643–653.
Zhou P, Byrne C, Jacobs J et al. Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. Genes Dev 1995; 9: 700–713.
Nakamura T, de Vega S, Fukumoto S et al. Transcription factor epiprofin is essential for tooth morphogenesis by regulating epithelial cell fate and tooth number. J Biol Chem 2008; 283: 4825–4833.
Nakamura T, Unda F, de-Vega S et al. The Kruppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation. J Biol Chem 2004; 279: 626–634.
Jarvinen E, Salazar-Ciudad I, Birchmeier W et al. Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signalling. Proc Natl Acad Sci USA 2006; 103: 18627–18632.
Liu F, Chu E Y, Watt B et al. Wnt/beta-catenin signalling directs multiple stages of tooth morphogenesis. Dev Biol 2008; 313: 210–224.
Groden J, Thliveris A, Samowitz W et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991; 66 : 589–600.
Novelli M R, Williamson J A, Tomlinson I P et al. Polyclonal origin of colonic adenomas in an XO/XY patient with FAP. Science 1996; 2 72: 1187–1190.
Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev 2007; 17: 45–51.
Chen Y, Bei M, Woo I et al. Msx1 controls inductive signalling in mammalian tooth morphogenesis. Development 1996; 122: 3035–3044.
Tucker A S, Al Khamis A, Sharpe P T. Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev Dyn 1998; 212: 533–539.
Vainio S, Karavanova I, Jowett A et al. Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 1993; 75: 45–58.
Munne P M, Tummers M, Jarvinen E et al. Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction. Development 2009; 136: 393–402.
Murashima-Suginami A, Takahashi K, Kawabata T et al. Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation. Biochem Biophys Res Commun 2007; 359 : 549–555.
Murashima-Suginami A, Takahashi K, Sakata T et al. Enhanced BMP signalling results in supernumerary tooth formation in USAG-1 deficient mouse. Biochem Biophys Res Commun 2008; 36 9: 1012–1016.
Melamed Y, Barkai G, Frydman M . Multiple supernumerary teeth (MSNT) and Ehlers-Danlos syndrome (EDS): a case report. J Oral Pathol Med 1994; 23: 88–91.
Cahuana A, Palma C, Gonzales W et al. Oral manifestations in Ellis-van Creveld syndrome: report of five cases. Pediatr Dent 2004; 26: 277–282.
Regattieri L R, Parker J L . Supernumerary teeth associated with Fabry-Anderson's syndrome. Oral Surg Oral Med Oral Pathol 1973; 35: 432–433.
Himelhoch D A, Scott B J, Olsen R A . Dental defects in incontinentia pigmenti: case report. Pediatr Dent 1987; 9: 236–239.
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Fleming, P., Xavier, G., DiBiase, A. et al. Revisiting the supernumerary: the epidemiological and molecular basis of extra teeth. Br Dent J 208, 25–30 (2010). https://doi.org/10.1038/sj.bdj.2009.1177
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DOI: https://doi.org/10.1038/sj.bdj.2009.1177