Amelogenesis Imperfecta: Current Understanding of Genotype-Phenotype

  • John Timothy WrightEmail author


There are nearly 100 hereditary conditions that affect enamel formation. Hereditary enamel conditions not associated with other tissue or developmental defects are traditionally referred to as amelogenesis imperfecta (AI). Enamel malformations involve either a deficiency in the amount of enamel (hypoplasia), a decrease in the mineral content or change in the composition of enamel (hypomineralization), or a combination of these two manifestations. The different amelogenesis imperfectas are challenging to diagnose and treat as they are extremely diverse in their clinical presentation and are genetically heterogeneous. There are multiple genes now known to cause AI and these different genes code for proteins that are critical for normal enamel formation. Ten genes with mutations known to cause AI have already been discovered, and the powerful new molecular technologies now available will help identify new genes that are associated with enamel defects. Understanding the etiology of hereditary conditions affecting enamel and how the enamel differs from normal (amount and/or composition) will allow clinicians to better advise their patients and select optimal treatment approaches.


Enamel Amelogenesis imperfecta Phenotype Genotype Gene Mutation 


  1. 1.
    Suckling G, Pearce E. Developmental defects of enamel in a group of New Zealand children: their prevalence and some associated etiological factors. Community Dent Oral Epidemiol. 1984;12:177–84.PubMedCrossRefGoogle Scholar
  2. 2.
    OMIM, Online Mendelian Inheritance in Man. Center for Medical Genetics, Johns Hopkins University and National Center for Biotechnology Information, National Library of Medicine, Baltimore; 2013.Google Scholar
  3. 3.
    Weinmann J, Svoboda J, Woods R. Hereditary disturbances of enamel formation and calcification. J Am Dent Assoc. 1945;32:397.Google Scholar
  4. 4.
    Witkop CJJ. Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited, problems in classification. J Oral Pathol. 1989;17:547–53.CrossRefGoogle Scholar
  5. 5.
    Rowley R, Hill FJ, Winter GB. An investigation of the association between anterior open-bite and amelogenesis imperfecta. Am J Orthod. 1982;81:229–35.PubMedCrossRefGoogle Scholar
  6. 6.
    Witkop CJ, Sauk JJ. Heritable defects of enamel. In: Stewart, Prescott G, editors. Oral facial genetics. St. Louis: R. C.V. Mosby Company; 1976. p. 151–226.Google Scholar
  7. 7.
    Witkop C, Kuhlamnn W, Sauk J. Autosomal recessive pigmented hypomaturation amelogenesis imperfecta. Oral Surg Oral Med Oral Pathol. 1973;36(3):367–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Crawford P, Aldred M. Amelogenesis imperfecta: autosomal dominant hypomaturation-hypoplasia type with taurodontism. Br Dent J. 1988;164:71–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Witkop CJ. Hereditary defects in enamel and dentin. Acta Genet. 1957;7:236–9.PubMedGoogle Scholar
  10. 10.
    Chosack A, et al. Amelogenesis imperfecta among Israeli Jews and the description of a new type of local hypoplastic autosomal recessive amelogenesis imperfecta. Oral Surg. 1979;47:148–56.PubMedCrossRefGoogle Scholar
  11. 11.
    Backman B. Amelogenesis imperfecta-clinical manifestations in 51 families in a northern Swedish country. Scand J Dent Res. 1988;96:505–16.PubMedGoogle Scholar
  12. 12.
    Backman B, Holm AK. Amelogenesis imperfecta: prevalence and incidence in a Northern Swedish County. Community Dent Oral Epidemiol. 1986;14:43–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Sundell S. Hereditary amelogenesis impertecta. An epidemiological, genetic and clinical study in a Swedish child population. Swed Dent J. 1986;31(Suppl):1–38.Google Scholar
  14. 14.
    Crawford PJ, Aldred M, Bloch-Zupan A. Amelogenesis imperfecta. Orphanet J Rare Dis. 2007;2:17.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Congleton J, Burkes E. Amelogenesis imperfecta with taurodontism. Oral Surg. 1979;48:540–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Wright JT, et al. Analysis of the tricho-dento-osseous syndrome genotype and phenotype. Am J Med Genet. 1997;72:197–204.PubMedCrossRefGoogle Scholar
  17. 17.
    Aldred MJ, Crawford PJM. Amelogenesis imperfecta-towards a new classification. Oral Dis. 1995;1:2–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Wright JT, et al. Amelogenesis imperfecta: genotype-phenotype studies in 71 families. Cells Tissues Organs. 2011;194(2–4):279–83.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Parry DA, et al. Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta. Am J Hum Genet. 2012;91(3):565–71.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Wright JT, et al. Relationship of phenotype and genotype in X-linked amelogenesis imperfecta. Connect Tissue Res. 2003;44(suppl):72–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Hart PS, et al. Establishment of a nomenclature for X-linked amelogenesis imperfecta. Archs Oral Biol. 2002;47:255–60.CrossRefGoogle Scholar
  22. 22.
    Nussier M, et al. Phenotypic diversity and revision of the nomenclature for autosomal recessive amelogenesis imperfecta. Oral Surg Oral Pathol Oral Med. 2004;97:220–30.CrossRefGoogle Scholar
  23. 23.
    Witkop CJJ. Partial expression of sex-linked amelogenesis imperfecta in females compatible with the Lyon hypothesis. Oral Surgery Oral Med Oral Pathol. 1967;23:174–82.CrossRefGoogle Scholar
  24. 24.
    Wright JT, et al. Enamel ultrastructure and protein content in X-linked amelogenesis imperfecta. Oral Surg Oral Med Oral Pathol. 1993;76(2):192–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Wright JT. The molecular etiologies and associated phenotypes of amelogenesis imperfecta. Am J Med Genet A. 2006;140(23):2547–55.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    El-Sayed W, et al. Ultrastructural analyses of deciduous teeth affected by hypocalcified amelogenesis imperfecta from a family with a novel Y458X FAM83H nonsense mutation. Cells Tissues Organs. 2010;191(3):235–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Kim JW, et al. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta. J Dent Res. 2013;92(10):899–904.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Jaureguiberry G, et al. Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations. Nephron Physiol. 2012;122(1–2):1–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Wang SK, et al. FAM20A mutations associated with enamel renal syndrome. J Dent Res. 2014;93(1):42–8.Google Scholar
  30. 30.
    Kantaputra PN, et al. Enamel-renal-gingival syndrome and FAM20A mutations. Am J Med Genet A. 2014;164A(1):1–9.Google Scholar
  31. 31.
    Kim JW, et al. ENAM mutations in autosomal-dominant amelogenesis imperfecta. J Dent Res. 2005;84(3):278–82.PubMedCrossRefGoogle Scholar
  32. 32.
    Hart PS, et al. Identification of the enamelin (g.8344delG) mutation in a new kindred and presentation of a standardized ENAM nomenclature. Archs Oral Biol. 2003;48:589–96.CrossRefGoogle Scholar
  33. 33.
    Hart TC, et al. Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localized enamel defects. J Med Genet. 2003;40:900–6.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Wright JT, Hall KI, Grubb BR. Enamel mineral composition of normal and cystic fibrosis transgenic mice. Adv Dent Res. 1996;10:270–4.PubMedCrossRefGoogle Scholar
  35. 35.
    El-Sayed W, et al. Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta. Am J Hum Genet. 2009;85(5):699–705.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Li W, et al. Reduced hydrolysis of amelogenin may result in X-linked amelogenesis imperfecta. Matrix Biol. 2001;19:7555–760.CrossRefGoogle Scholar
  37. 37.
    Ravassipour DB, et al. Unique enamel phenotype associated with amelogenin gene (AMELX) codon 41 point mutation. J Dent Res. 2000;79:1476–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Simmer JP, Hu JC. Expression, structure, and function of enamel proteinases. Connect Tissue Res. 2002;43(2–3):441–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Robinson C, Weatherell JA, Hallsworth AS. Variations in the composition of dental enamel within thin ground sections. Caries Res. 1971;5:44–57.PubMedCrossRefGoogle Scholar
  40. 40.
    Wright JT, Hall KI, Yamauchi M. The enamel proteins in human amelogenesis imperfecta. Archs Oral Biol. 1997;42:149–59.CrossRefGoogle Scholar
  41. 41.
    Wright JT, et al. The mineral and protein content of enamel in amelogenesis imperfecta. Connect Tissue Res. 1995;31:247–52.CrossRefGoogle Scholar
  42. 42.
    Seow WK. Taurodontism of the mandibular first permanent molar distinguishes between the tricho-dento-osseous (TDO) syndrome and amelogenesis imperfecta. Clin Genet. 1993;43:240–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Crawford PJM, Aldred MJ. Amelogenesis imperfecta with taurodontism and the tricho-dento-osseous syndrome: separate conditions or a spectrum of disease? Clin Genet. 1990;38:44–50.PubMedCrossRefGoogle Scholar
  44. 44.
    Wright JT, et al. Phenotypic variability of the tricho-dento-osseous syndrome associated with a DLX3 homeobox gene mutation. In: Chemistry and biology of mineralized tissues. Proceedings of the sixth international conference. Goldberg M, Boskey A, Robinson C, editors. Amer Acad Orthoped Surg: Rosemont; 2000. p. 27–31.Google Scholar
  45. 45.
    Dong J, et al. DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. Am J Med Genet A. 2005;133A(2):138–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Wright JT, et al. DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome. Am J Med Genet A. 2008;146(3):343–9.CrossRefGoogle Scholar
  47. 47.
    Persson M, Sundell S. Facial morphology and open bite deformity in amelogenesis imperfecta. Acta Odontol Scand. 1982;40:135–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Cartwright AR, Kula K, Wright JT. Craniofacial features associated with amelogenesis imperfecta. J Craniofac Genet Dev Biol. 1999;19:148–56.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Pediatric DentistryUniversity of North Carolina, School of DentistryChapel HillUSA

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