MOLAR INCISOR HYPOMINERALIZATION

cocukdishekimligiozel11-1-25kapakv2

Etiology, Genetic Background and Epidemiology of Molar Incisor Hypomineralization

Elif Bahar TUNA İNCEa
aİstanbul University Faculty of Dentistry, Department of Pediatric Dentistry, İstanbul, Türkiye

Tuna İnce EB. Etiology, genetic background and epidemiology of molar incisor hypomineralization. In: Şen Tunç E, ed. Molar Incisor Hypomineralization. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.1-7.

ABSTRACT
Molar incisor hypomineralization (MIH) is a common developmental dental defect that emerges during childhood. In MIH cases, one or more permanent first molars are affected, and permanent incisors are often involved as well. Although the exact cause of MIH remains unknown, current evidence suggests that MIH has a multifactorial etiology. A genetically predisposed background involving multiple coding genes constitutes only one of the many contributing factors. Additionally, MIH is thought to be associated with environmental risk factors such as malnutrition, medications, respiratory problems, and infections. Since MIH was first defined as a distinct clinical condition in 2001, numerous studies have been conducted worldwide to determine its prevalence in both general and clinical populations. The aim of this review is to provide an up-to-date assessment of the epidemiology, etiology, and genetic background of MIH.

Keywords: Dental enamel hypoplasia; epidemiology; etiology

Referanslar

  1. Elhennawy K, Anang M, Splieth C, Bekes K, Manton DJ, Hedar Z, et al. Knowledge, attitudes, and beliefs regarding molar incisor hypomineralization (MIH) amongst German dental students. International Journal of Paediatric Dentistry. 2021;31(4);486-95. [Crossref]  [PubMed]
  2. Bezamat M, Souza JF, Silva FMF, Correa EG, Fatturi AL, Brancher JA, et al. Gene-environment interaction in molar-incisor hypomineralization. PLoS ONE. 2021;16(1):e0241898. [Crossref]  [PubMed]  [PMC]
  3. Crombie F, Manton D, Kilpatrick N. Aetiology of molar-incisor hypomineralization: a critical review. Int J Paediatr Dent. 2009;19(2):73-83. [Crossref]  [PubMed]
  4. Alaluusua S. Aetiology of Molar-Incisor Hypomineralisation: a systematic review. Eur Arch Paediatr Dent. 2010;11(2):53-8. [Crossref]  [PubMed]
  5. Silva MJ, Scurrah KJ, Craig JM, Manton DJ, Kilpatrick N. Etiology of Molar Incisor Hypomineralization - a systematic review. Community Dent Oral Epidemiol. 2016;44(4):342-53. [Crossref]  [PubMed]
  6. Kühnisch J, Thiering E, Kratzsch J, Heinrich-Weltzien R, Hickel R, Heinrich J; GINIplus study group; LISAplus study group. Elevated serum 25(OH)-vitamin D levels are negatively correlated with molar-incisor hypomineralization. J Dent Res. 2015;94(2):381-7. [Crossref]  [PubMed]  [PMC]
  7. Bekes K. Molar Incisor Hypomineralization A Clinical Guide to Diagnosis and Treatment. Springer Nature Switzerland AG; 2020. p.190. [Crossref]
  8. Wright JT, Carrion IA, Morris C. The molecular basis of hereditary enamel defects in humans. J Dent Res. 2015;94(1):52-61. [Crossref]  [PubMed]  [PMC]
  9. Lacruz R, Habelitz S, Wright J, Paine M. Dental enamel formation and implications for oral health and disease. Physiol Rev. 2017;97(3):939-93. [Crossref]  [PubMed]  [PMC]
  10. Seymen F, Park JC, Lee KE, Lee HK, Lee DS, Koruyucu M, et al. Novel MMP20 and KLK4 Mutations in Amelogenesis Imperfecta. J Dent Res. 2015;94(8):1063-9. [Crossref]  [PubMed]
  11. Chun YP, Tan C, Villanueva O, Colley ME, Quintanilla TJ, Basiouny MS, et al. Overexpression of ameloblastin in secretory ameloblasts results in demarcated, hypomineralized opacities in enamel. Front Physiol. 2024;14:1233391. [Crossref]  [PubMed]  [PMC]
  12. Kim JW, Lee SK, Lee ZH, Park JC, Lee KE, Lee MH, et al. FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet. 2008;82:489-94. [Crossref]  [PubMed]  [PMC]
  13. Crawford PJM, Aldred M, Bloch-Zupan A. Amelogenesis imperfecta. Orphanet J Rare Dis. 2007;2:17-27. [Crossref]  [PubMed]  [PMC]
  14. Crombie FA, Manton DJ, Palamara JEA, Zalizniak I, Cochrane NJ, Reynolds EC. Characterisation of developmentally hypomineralised human enamel. J Dent. 2013;41(7):611-8. [Crossref]  [PubMed]
  15. Bronckers ALJJ. Ion transport by ameloblasts during amelogenesis. J Dent Res. 2017;96(3):243-53. [Crossref]  [PubMed]
  16. Pham CD, Smith CE, Hu Y, Hu JC, Simmer JP, Chun YP. Endocytosis and Enamel Formation. Front Physiol. 2017;8:529. [Crossref]  [PubMed]  [PMC]
  17. Rácz R, Földes A, Bori E, Zsembery Á, Harada H, Steward MC, et al. No change in bicarbonate transport but tight-junction formation is delayed by fluoride in a novel ameloblast model. Front Physiol. 2017;8:940. [Crossref]  [PubMed]  [PMC]
  18. Couwenhoven RI, Davis C, Snead ML. Mouse ameloblasts do not transcribe the albumin gene. Calcif Tissue Int. 1989;45(6):367-71. [Crossref]  [PubMed]
  19. Robinson C, Brookes SJ, Kirkham J, Bonass WA, Shore RC. Crystal growth in dental enamel:the role of amelogenins and albumin. Adv Dent Res. 1996;10(2):173-80. [Crossref]  [PubMed]
  20. Robinson C, Kirkham J, Brookes SJ, Shore RC. The role of albumin in developing rodent dental enamel: a possible explanation for white spot hypoplasia. J Dent Res. 1992;71(6):1270-4. [Crossref]  [PubMed]
  21. Robinson C, Shore RC, Kirkham J, Stonehouse NJ. Extracellular processing of enamel matrix proteins and the control of crystal growth. J Biol Buccale. 1990;18(4):355-61.
  22. Suzuki M, Shin M, Simmer JP, Bartlett JD. Fluoride affects enamel protein content via TGF-β1-mediated KLK4 inhibition. J Dent Res. 2014;93(10):1022-7. [Crossref]  [PubMed]  [PMC]
  23. Zhang LW, Cong X, Zhang Y, Wei T, Su YC, Serrão ACA, et al. Interleukin-17 impairs salivary tight junction integrity in Sjögren's syndrome. J Dent Res. 2016;95(7):784-92. [Crossref]  [PubMed]
  24. Zhuang Y, Hu C, Ding G, Zhang Y, Huang S, Jia Z, et al. Albumin impairs renal tubular tight junctions via targeting the NLRP3 inflammasome. Am J Physiol Renal Physiol. 2015;308(9):F1012-9. [Crossref]  [PubMed]
  25. Chang C-W, Wang X, Caldwell RB. Serum opens tight junctions and reduces ZO-1 protein in retinal epithelial cells. J Neurochem. 1997;69(2):859-67. [Crossref]  [PubMed]
  26. Lacruz RS, Habelitz S, Wright JT, Paine ML. Transcriptomics of enamel matrix-forming cells: Ameloblasts as models for biomineralization research. Front Physiol. 2017;8:974.
  27. Suckling G, et al. Developmental defects of enamel: A biological basis. Advances in Dental Research. 1989;3(2):188-93. [Crossref]  [PubMed]
  28. Jeremias F, Koruyucu M, Küchler EC, Bayram M, Tuna EB, Deeley K, et al. Genes expressed in dental enamel development are associated with molar-incisor hypomineralization. Arch Oral Biol. 2013;58(10):1434-42. [Crossref]  [PubMed]  [PMC]
  29. Vieira AR. On the genetics contribution to molar incisor hypomineralization. Int J Paediatr Dent. 2019;29(1):2-3. [Crossref]  [PubMed]
  30. Teixeira R, Andrade NS, Queiroz LCC, Mendes FM, Moura MS, Moura L, et al. Exploring the association between genetic and environmental factors and molar incisor hypomineralization: evidence from a twin study. Int J Paediatr Dent. 2018;28(2):198-206. [Crossref]  [PubMed]
  31. Silva MJ, Kilpatrick NM, Craig JM, Manton DJ, Leong P, Burgner D, et al. Etiology of hypomineralized second primary molars: a prospective twin study. J Dent Res. 2019;98(1):77-83. [Crossref]  [PubMed]  [PMC]
  32. Kuhnisch J, Thiering E, Heitmuller D, Tiesler CMT, Grallert H, Heinrich-Weltzien R, et al. Genome-wide association study (GWAS) for molar-incisor hypomineralization (MIH). Clin Oral Investig. 2014;18(2):677-82. [Crossref]  [PubMed]
  33. Bussaneli DG, Restrepo M, Fragelli CMB, Santos-Pinto L, Jeremias F, Cordeiro RCL, al. Genes regulating immune response and amelogenesis interact in increasing the susceptibility to molar-incisor hypomineralization. Caries Res. 2019;53(2):217-27. [Crossref]  [PubMed]
  34. Kobayashi-Kinoshita S, Yamakoshi Y, Onuma K, Yamamoto R, Asada Y. TGF-β1 autocrine signalling and enamel matrix components. Sci Rep. 2016;6:33644. [Crossref]  [PubMed]  [PMC]
  35. Frascino S, Frascino A, Rezende KM, Imparato JC, Pignatari S. Molar-incisor enamel hypomineralization cross-sectional prevalence evaluation in oral-breathing allergic children. Clin Lab Res Dent. 2017;1-6. [Crossref]
  36. Townsend G, Richards L, Hughes T, Pinkerton S, Schwerdt W. Epigenetic influences may explain dental differences in monozygotic twin pairs. Aust Dent J. 2005;50(2):95-100. [Crossref]  [PubMed]
  37. Wang J, Sun K, Shen Y, Xu Y, Xie J, Huang R, et al. DNA methylation is critical for tooth agenesis: implications for sporadic non-syndromic anodontia and hypodontia. Sci Rep. 2016;6:19162. [Crossref]  [PubMed]  [PMC]
  38. Wuollet E, Laisi S, Salmela E, Ess A, Alaluusua S. Background factors of molar-incisor hypomineralization in a group of Finnish children. Acta Odontol Scand. 2014;72(8):963-9. [Crossref]  [PubMed]
  39. Ngoc VTN, Huong LT, Van Nhon B, Tan NTM, Van Thuc P, Hien VTT, et al. The higher of developmental defects of enamel in the dioxin-affected region than non-dioxin-affected region: result from a cross-sectional study in Vietnam. Odontology. 2019;107(1):17-22. [Crossref]  [PubMed]
  40. Jedeon K, Berdal A, Babajko S. Impact of three endocrine disruptors, Bisphenol a, Genistein and Vinclozolin on female rat enamel. Bull Group Int Rech Sci Stomatol Odontol. 2016;53(1):28-32.
  41. Weerheijm KL, Jälevik B, Alaluusua S. Molar-incisor hypomineralisation. Caries Res. 2001;35(5):390-1. [Crossref]  [PubMed]
  42. Mori M, Clausson CM, Sanden C, Jönsson J, Andersson CK, Siddhuraj P, et al. Expansion of Phenotypically Altered Dendritic Cell Populations in the Small Airways and Alveolar Parenchyma in Patients with Chronic Obstructive Pulmonary Disease. J Innate Immun. 2023;15(1):188-203. [Crossref]  [PubMed]  [PMC]
  43. van der Tas JT, Elfrink MEC, Heijboer AC, Rivadeneira F, Jaddoe VWV, Tiemeier H, et al. Foetal, neonatal and child vitamin D status and enamel hypomineralization. Community Dentist Oral Epidemiol. 2018;46(4):343-51. [Crossref]  [PubMed]  [PMC]
  44. Ghanim A, Silva MJ, Elfrink MEC, Lygidakis NA, Mariño RJ, Weerheijm KL, et al. Molar incisor hypomineralisation (MIH) training manual for clinical field surveys and practice. Eur Arch Paediatr Dent. 2017;18(4):225-42. [Crossref]  [PubMed]
  45. Zhao D, Dong B, Yu D, Ren Q, Sun Y. The prevalence of molar incisor hypomineralization: evidence from 70 studies. Int J Paediatr Dent. 2018;28(2):170-9. [Crossref]  [PubMed]
  46. Sezer B, Çarıkçıoğlu B. Treatment Strategies for Incisors of Children Affected by Molar Incisor Hypomineralization: A Narrative Review. Oral. 2024;4(1):74-89. [Crossref]