The Human Genetics of Dental Anomalies

Abstract

The development of tooth is a highly complex procedure and mastered by specific genetic programs. Genetic alterations, environmental factors, and developmental timing can disturb the execution of these programs, and result in various dental anomalies like hypodontia/oligodontia, and supernumerary teeth, which are commonly seen in our clinical practice. Advances in molecular research enabled the identification of various genes involved in the pathogenesis of dental anomalies. In the near future, it will help provide a more accurate diagnosis and biological-based treatment for these anomalies. In this article, we present the molecular phenomenon of tooth development and the genetics of various dental anomalies.

Keywords

tooth development / dental anomalies / genetics / genes / mutations

References

[1] Galluccio G, Castellano M, La Monaca C.Genetic basis of non-syndromic anomalies of human tooth number. Arch Oral Biol 2012; 57(07): 918-930

[2] Brook AH.Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Arch Oral Biol 2009; 54(Suppl. 01): S3-S17

[3] de La Dure-Molla M, Fournier BP, Manzanares MC.et al; International Group of Dental Nomenclature. Elements of morphology: standard terminology for the teeth and classifying genetic dental disorders. Am J Med Genet A 2019; 179(10): 1913-1981

[4] Cakan DG, Ulkur F, Taner T.The genetic basis of dental anomalies and its relation to orthodontics. Eur J Dent 2013; 7(Suppl. 01): S143-S147

[5] Vastardis H.The genetics of human tooth agenesis: new discoveries for understanding dental anomalies. Am J Orthod Dentofacial Orthop 2000; 117(06): 650-656

[6] Klein OD, Oberoi S, Huysseune A, Hovorakova M, Peterka M, Peterkova R.Developmental disorders of the dentition: an update. Am J Med Genet C Semin Med Genet 2013; 163C(04): 318-332

[7] Thesleff I.Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci 2003; 116(Pt 9): 1647-1648

[8] Bailleul-Forestier I, Molla M, Verloes A, Berdal A.The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders. Eur J Med Genet 2008; 51(04): 273-291

[9] Thesleff I.The genetic basis of tooth development and dental defects. Am J Med Genet A 2006; 140(23): 2530-2535

[10] Thesleff I.The genetic basis of normal and abnormal craniofacial development. Acta Odontol Scand 1998; 56(06): 321-325

[11] Diekwisch TG.Pathways and fate of migratory cells during late tooth organogenesis. Connect Tissue Res 2002; 43(2-3): 245-256

[12] Sharpe PT.Neural crest and tooth morphogenesis. Adv Dent Res 2001; 15: 4-7

[13] Lisi S, Peterková R, Peterka M, Vonesch JL, Ruch JV, Lesot H.Tooth morphogenesis and pattern of odontoblast differentiation. Connect Tissue Res 2003; 44(Suppl. 01): 167-170

[14] Matalova E, Fleischmannova J, Sharpe PT, Tucker AS.Tooth agenesis: from molecular genetics to molecular dentistry. J Dent Res 2008; 87(07): 617-623

[15] Kavitha B, Priyadharshini V, Sivapathasundharam B, Saraswathi TR.Role of genes in oro-dental diseases. Indian J Dent Res 2010; 21(02): 270-274

[16] Cobourne MT.Familial human hypodontia: is it all in the genes?. Br Dent J 2007; 203(04): 203-208

[17] Sharpe PT.Homeobox genes and orofacial development. Connect Tissue Res 1995; 32(1-4): 17-25

[18] Thesleff I.Homeobox genes and growth factors in regulation of craniofacial and tooth morphogenesis. Acta Odontol Scand 1995; 53(03): 129-134

[19] Neubüser A, Peters H, Balling R, Martin GR.Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation. Cell 1997; 90(02): 247-255

[20] Mostowska A, Biedziak B, Zadurska M, Dunin-Wilczyńska I, Lianeri M, Jagodziński PP.Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non-syndromic tooth agenesis. Clin Genet 2013; 84(05): 429-440

[21] James MJ, Järvinen E, Wang XP, Thesleff I.Different roles of Runx2 during early neural crest-derived bone and tooth development. J Bone Miner Res 2006; 21(07): 1034-1044

[22] Merametdjian L, Prud'Homme T, Le Caignec C, Isidor B, Lopez-Cazaux S. Oro-dental phenotype in patients with RUNX2 duplication. Eur J Med Genet 2019; 62(02): 85-89

[23] De Coster PJ, Marks LA, Martens LC, Huysseune A.Dental agenesis: genetic and clinical perspectives. J Oral Pathol Med 2009; 38(01): 1-17

[24] Rakhshan V.Congenitally missing teeth (hypodontia): a review of the literature concerning the etiology, prevalence, risk factors, patterns and treatment. Dent Res J (Isfahan) 2015; 12(01): 1-13

[25] Soni HK, Joshi M, Desai H, Vasavada M.An orthopantomographic study of prevalence of hypodontia and hyperdontia in permanent dentition in Vadodara, Gujarat. Indian J Dent Res 2018; 29(04): 529-533

[26] Jurek A, Gozdowski D, Zadurska M.Agenesis of permanent teeth: a report based on cases from clinical practice. Forum Ortod 2019; 15: 263-271

[27] Gerits A, Nieminen P, De Muynck S, Carels C.Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe oligodontia phenotype. Orthod Craniofac Res 2006; 9(03): 129-136

[28] Vieira AR, Meira R, Modesto A, Murray JC.MSX1, PAX9, and TGFA contribute to tooth agenesis in humans. J Dent Res 2004; 83(09): 723-727

[29] Lidral AC, Reising BC.The role of MSX1 in human tooth agenesis. J Dent Res 2002; 81(04): 274-278

[30] Vastardis H, Karimbux N, Guthua SW, Seidman JG, Seidman CE.A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nat Genet 1996; 13(04): 417-421

[31] Kim JW, Simmer JP, Lin BP, Hu JC.Novel MSX1 frameshift causes autosomal-dominant oligodontia. J Dent Res 2006; 85(03): 267-271

[32] Stockton DW, Das P, Goldenberg M, D'Souza RN, Patel PI. Mutation of PAX9 is associated with oligodontia. Nat Genet 2000; 24(01): 18-19

[33] Kapadia H, Mues G, D'Souza R. Genes affecting tooth morphogenesis. Orthod Craniofac Res 2007; 10(03): 105-113

[34] Peters H, Neubüser A, Balling R.Pax genes and organogenesis: Pax9 meets tooth development. Eur J Oral Sci 1998; 106(Suppl. 01): 38-43

[35] Brook AH, Elcock C, Aggarwal M.et al.Tooth dimensions in hypodontia with a known PAX9 mutation. Arch Oral Biol 2009; 54(Suppl. 01): S57-S62

[36] Nieminen P, Arte S, Tanner D.et al.Identification of a nonsense mutation in the PAX9 gene in molar oligodontia. Eur J Hum Genet 2001; 9(10): 743-746

[37] Klein ML, Nieminen P, Lammi L, Niebuhr E, Kreiborg S.Novel mutation of the initiation codon of PAX9 causes oligodontia. J Dent Res 2005; 84(01): 43-47

[38] Mostowska A, Kobielak A, Trzeciak WH.Molecular basis of non-syndromic tooth agenesis: mutations of MSX1 and PAX9 reflect their role in patterning human dentition. Eur J Oral Sci 2003; 111(05): 365-370

[39] Lammi L, Arte S, Somer M.et al.Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004; 74(05): 1043-1050

[40] Polder BJ, Van't Hof MA, Van der Linden FP, Kuijpers-Jagtman AM. A meta-analysis of the prevalence of dental agenesis of permanent teeth. Community Dent Oral Epidemiol 2004; 32(03): 217-226

[41] Kantaputra P, Sripathomsawat W.WNT10A and isolated hypodontia. Am J Med Genet A 2011; 155A(05): 1119-1122

[42] Song S, Han D, Qu H.et al.EDA gene mutations underlie non-syndromic oligodontia. J Dent Res 2009; 88(02): 126-131

[43] Khabour OF, Mesmar FS, Al-Tamimi F, Al-Batayneh OB, Owais AI.Missense mutation of the EDA gene in a Jordanian family with X-linked hypohidrotic ectodermal dysplasia: phenotypic appearance and speech problems. Genet Mol Res 2010; 9(02): 941-948

[44] Tao R, Jin B, Guo SZ.et al.A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia. J Hum Genet 2006; 51(05): 498-502

[45] Han D, Gong Y, Wu H.et al.Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis. Eur J Med Genet 2008; 51(06): 536-546

[46] Subasioglu A, Savas S, Kucukyilmaz E, Kesim S, Yagci A, Dundar M.Genetic background of supernumerary teeth. Eur J Dent 2015; 9(01): 153-158

[47] Wang XP, Fan J.Molecular genetics of supernumerary tooth formation. Genesis 2011; 49(04): 261-277

[48] Anthonappa RP, King NM, Rabie AB.Aetiology of supernumerary teeth: a literature review. Eur Arch Paediatr Dent 2013; 14(05): 279-288

[49] Solares R, Romero MI.Supernumerary premolars: a literature review. Pediatr Dent 2004; 26(05): 450-458

[50] Küchler EC, Costa AG, Costa MdeC, Vieira AR, Granjeiro JM. Supernumerary teeth vary depending on gender. Braz Oral Res 2011; 25(01): 76-79

[51] Cohen Jr MM.Biology of RUNX2 and cleidocranial dysplasia. J Craniofac Surg 2013; 24(01): 130-133

[52] Inchingolo F, Tatullo M, Abenavoli FM.et al.Non-syndromic multiple supernumerary teeth in a family unit with a normal karyotype: case report. Int J Med Sci 2010; 7(06): 378-384

[53] Bäckman B, Holmgren G.Amelogenesis imperfecta: a genetic study. Hum Hered 1988; 38(04): 189-206

[54] Nusier M, Yassin O, Hart TC, Samimi A, Wright JT.Phenotypic diversity and revision of the nomenclature for autosomal recessive amelogenesis imperfecta. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 97(02): 220-230

[55] Greene SR, Yuan ZA, Wright JT.et al.A new frameshift mutation encoding a truncated amelogenin leads to X-linked amelogenesis imperfecta. Arch Oral Biol 2002; 47(03): 211-217

[56] Dong J, Gu TT, Simmons D, MacDougall M. Enamelin maps to human chromosome 4q21 within the autosomal dominant amelogenesis imperfecta locus. Eur J Oral Sci 2000; 108(05): 353-358

[57] Ozdemir D, Hart PS, Firatli E, Aren G, Ryu OH, Hart TC.Phenotype of ENAM mutations is dosage-dependent. J Dent Res 2005; 84(11): 1036-1041

[58] Kim JW, Simmer JP, Hart TC.et al.MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet 2005; 42(03): 271-275

[59] Hart PS, Hart TC, Michalec MD.et al.Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet 2004; 41(07): 545-549

[60] Dong J, Amor D, Aldred MJ, Gu T, Escamilla M, MacDougall M. DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. Am J Med Genet A 2005; 133A(02): 138-141

[61] Wright JT, Kula K, Hall K, Simmons JH, Hart TC.Analysis of the tricho-dentoosseous syndrome genotype and phenotype. Am J Med Genet 1997; 72(02): 197-204

[62] Hu JC, Simmer JP.Developmental biology and genetics of dental malformations. Orthod Craniofac Res 2007; 10(02): 45-52

[63] Hart PS, Hart TC.Disorders of human dentin. Cells Tissues Organs 2007; 186(01): 70-77

[64] MacDougall M, Jeffords LG, Gu TT.et al. Genetic linkage of the dentinogenesis imperfecta type III locus to chromosome 4q. J Dent Res 1999; 78(06): 1277-1282

[65] Barron MJ, McDonnell ST, Mackie I, Dixon MJ. Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia. Orphanet J Rare Dis 2008; 3: 31

[66] Lee SK, Lee KE, Jeon D.et al.A novel mutation in the DSPP gene associated with dentinogenesis imperfecta type II. J Dent Res 2009; 88(01): 51-55

[67] Surendra P, Shah R, Roshan NM, Reddy VVS.Dentinogenesis imperfecta: a family which was affected for over three generations. J Clin Diagn Res 2013; 7(08): 1808-1811

[68] Zhang X, Zhao J, Li C.et al.DSPP mutation in dentinogenesis imperfecta Shields type II. Nat Genet 2001; 27(02): 151-152

[69] Rios D, Vieira AL, Tenuta LM, Machado MA.Osteogenesis imperfecta and dentinogenesis imperfecta: associated disorders. Quintessence Int 2005; 36(09): 695-701

[70] MacDonald D. Taurodontism. Oral Radiol 2020; 36(02): 129-132

[71] Gomes RR, Habckost CD, Junqueira LG.et al.Taurodontism in Brazilian patients with tooth agenesis and first and second-degree relatives: a case-control study. Arch Oral Biol 2012; 57(08): 1062-1069

[72] Jayashankara C, Shivanna AK, Sridhara K, Kumar PS.Taurodontism: a dental rarity. J Oral Maxillofac Pathol 2013; 17(03): 478

[73] Chetty M, Roomaney IA, Beighton P.Taurodontism in dental genetics. BDJ Open 2021; 7(01): 25

[74] Whitehouse LLE, Smith CEL, Poulter JA.et al.Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome. Oral Dis 2019; 25(01): 182-191

[75] Andersson EM, Axelsson S, Gjølstad LF, Storhaug K.Taurodontism: a minor diagnostic criterion in Laurence-Moon/Bardet-Biedl syndromes. Acta Odontol Scand 2013; 71(06): 1671-1674

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