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Dental and oral anomalies in incontinentia pigmenti: a systematic review

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Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by a mutation of the IKBKG gene. The objective of this study was to present a systematic review of the dental and oral types of anomalies, to determine the total number and sex distribution of the anomalies, and to analyze possible therapies.

Materials and methods

We analyzed the literature data from 1,286 IP cases from the period 1993–2010.


Dental and/or oral anomalies were diagnosed for 54.38% of the investigated IP patients. Most of the anomaly types were dental, and the most frequent of these were dental shape anomalies, hypodontia, and delayed dentition. The most frequent oral anomaly types were cleft palate and high arched palate. IKBKG exon 4–10 deletion was present in 86.36% of genetically confirmed IP patients.


According to the frequency, dental and/or oral anomalies represent the most frequent and important IP minor criteria. The most frequent mutation was IKBKG exon 4–10 deletion. The majority of dental anomalies and some of the oral anomalies could be corrected.

Clinical relevance

Because of the presence of cleft palate and high arched palate in IP patients, these two anomalies may be considered as diagnostic IP minor criteria as well.

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Incontinentia pigmenti


Inhibitor of kappa B kinase gamma


NF-κB essential modulator


Nuclear factor-kappa B


  1. Berlin A, Paller AS, Chan LS (2002) Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology. J Am Acad Dermatol 47:169–187. doi:10.1067/mjd.2002.125949

    Article  PubMed  Google Scholar 

  2. Orphanet Report Series. Rare diseases collection. May 2011, No. 1. Prevalence of rare diseases: bibliographic data. Accessed 9 Nov 2011

  3. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, Israël A, Heiss NS, Klauck SM, Kioschis P, Wiemann S, Poustka A, Esposito T, Bardaro T, Gianfrancesco F, Ciccodicola A, D’Urso M, Woffendin H, Jakins T, Donnai D, Stewart H, Kenwrick SJ, Aradhya S, Yamagata T, Levy M, Lewis RA, Nelson DL (2000) Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 405:466–472. doi:10.1038/35013114

    Article  PubMed  Google Scholar 

  4. Courtois G, Gilmore TD (2006) Mutations in the NF-κB signaling pathway: implication for human disease. Oncogene 25:6831–6843. doi:10.1038/sj.onc.1209939

    Article  PubMed  Google Scholar 

  5. Orange JS, Levy O, Geha RS (2005) Human disease resulting from gene mutations that interfere with appropriate nuclear factor-κB activation. Immunol Rev 203:21–37. doi:10.1111/j.0105-2896.2005.00221.x

    Article  PubMed  Google Scholar 

  6. Scheuerle A, Ursini MV. Incontinentia pigmenti (Bloch–Sulzberger syndrome). University of Washington, Seattle (WA): GeneReviews 2008 Feb, 22 pp. Accessed 28 Oct 2010

  7. Fusco F, Paciolla M, Napolitano F, Pescatore A, D’Addario I, Bal E, Lioi MB, Smahi A, Miano MG, Ursini MV (2012) Genomic architecture at the incontinentia pigmenti locus favours de novo pathological alleles through different mechanisms. Hum Mol Genet 1:1260–1271. doi:10.1093/hmg/ddr556

    Article  Google Scholar 

  8. Fusco F, Bardaro T, Fimiani G, Mercadante V, Miano MG, Falco G, Israël A, Courtois G, D’Urso M, Ursini MV (2004) Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-κB activation. Hum Mol Genet 13:1763–1773. doi:10.1093/hmg/ddh192

    Article  PubMed  Google Scholar 

  9. Landy SJ, Donnai D (1993) Incontinentia pigmenti (Bloch–Sulzberger syndrome). J Med Genet 30:53–59

    Article  PubMed  Google Scholar 

  10. Garcia-Dorado J, de Unamuno P, Fernandez-Lopez E, Salazar Veloz J, Armijo M (1990) Incontinentia pigmenti: XXY male with a family history. Clin Genet 38:128–138

    Article  PubMed  Google Scholar 

  11. Hadj-Rabia S, Rimella A, Smahi A, Fraitag S, Hamel-Teillac D, Bonnefont JP, de Prost Y, Bodemer C (2011) Clinical and histologic features of incontinentia pigmenti in adults with nuclear factor-κB essential modulator gene mutations. J Am Acad Dermatol 64:508–515. doi:10.1016/j.jaad.2010.01.045

    Article  PubMed  Google Scholar 

  12. Garrod AE (1906) Peculiar pigmentation of the skin of an infant. Trans Clin Soc London 39:216

    Google Scholar 

  13. Carney RG (1976) Incontinentia pigmenti: a world statistical analysis. Arch Dermatol 112:535–542

    Article  PubMed  Google Scholar 

  14. Parrish JE, Scheuerle AE, Lewis RA, Levy ML, Nelson DL (1996) Selection against mutant alleles in blood leukocytes is a consistent feature in incontinentia pigmenti type 2. Hum Mol Genet 5:1777–1783. doi:10.1093/hmg/5.11.1777

    Article  PubMed  Google Scholar 

  15. Minić S, Novotny GEK, Trpinac D, Obradović M (2006) Clinical features of incontinentia pigmenti with emphasis on oral and dental abnormalities. Clin Oral Invest 10:343–347. doi:10.1007/s00784-006-0066-z

    Article  Google Scholar 

  16. Phan TA, Wargon O, Turner AM (2005) Incontinentia pigmenti case series: clinical spectrum of incontinentia pigmenti in 53 female patients and their relatives. Clin Exp Dermatol 30:474–480. doi:10.1111/j.1365-2230.2005.01848.x

    Article  PubMed  Google Scholar 

  17. Holmström G, Bergendal B, Hallberg G, Marcus S, Hallén A, Dahl N (2002) Incontinentia pigmenti—a rare disease with many symptoms. Lakartidningen 99:1345–1350

    PubMed  Google Scholar 

  18. Hadj-Rabia S, Froidevaux D, Bodak N, Hamel-Teillac D, Smahi A, Touil Y, Fraitag S, de Prost Y, Bodemer C (2003) Clinical study of 40 cases of incontinentia pigmenti. Arch Dermatol 139:1163–1170

    Article  PubMed  Google Scholar 

  19. Sachs L (1984) Applied statistics, 2nd edn. Springer, New York

    Book  Google Scholar 

  20. Mansour S, Woffendin H, Mitton S, Jeffery I, Jakins T, Kenwrick S, Murday VA (2001) Incontinentia pigmenti in a surviving male is accompanied by hypohidrotic ectodermal dysplasia and recurrent infection. Am J Med Genet 99:172–177. doi:10.1002/1096-8628(2001) 9999:9999<::AID-AJMG1155>3.0.CO;2-Y

    Article  PubMed  Google Scholar 

  21. Dupuis-Girod S, Corradini N, Hadj-Rabia S, Fournet JC, Faivre L, Le Deist F, Durand P, Döffinger R, Smahi A, Israël A, Courtois G, Brousse N, Blanche S, Munnich A, Fischer A, Casanova JL, Bodemer C (2002) Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother. Pediatrics 109:e97. doi:10.1542/peds.109.6.e97

    Article  PubMed  Google Scholar 

  22. Rola M, Martins T, Melo MJ, Gomes R, Roseira J, Souto A (2004) Incontinence of pigment. An Pediatr (Barc) 60:601–602

    Article  Google Scholar 

  23. Zou CC, Zhao ZY (2007) Clinical and molecular analysis of NF-κB essential modulator in Chinese incontinentia pigmenti patients. Int J Dermatol 46:1017–1022. doi:10.1111/j.1365-4632.2007.03365.x

    Article  PubMed  Google Scholar 

  24. Yonezu T, Hayashi Y, Sasaki J, Machida Y (1997) Prevalence of congenital dental anomalies of the deciduous dentition in Japanese children. Bull Tokyo Dent Coll 38:27–32

    PubMed  Google Scholar 

  25. Polder BJ, Van’t Hof MA, Van der Linden FPGM, Kuijpers-Jagtman AM (2004) A meta-analysis of the prevalence of dental agenesis of permanent teeth. Community Dent Oral Epidemiol 32:217–226. doi:10.1111/j.1600-0528.2004.00158.x

    Article  PubMed  Google Scholar 

  26. Himelhoch DA, Scott BJ, Olsen RA (1987) Dental defects in incontinentia pigmenti: case report. Pediatr Dent 9:236–239

    PubMed  Google Scholar 

  27. Macey-Dare LV, Goodman JR (1999) Incontinentia pigmenti: seven cases with dental manifestations. Int J Paediatr Dent 9:293–297

    Article  PubMed  Google Scholar 

  28. Bentolila R, Rivera H, Sanchez-Quevedo MC (2006) Incontinentia pigmenti: a case report. Pediatr Dent 28:54–57

    PubMed  Google Scholar 

  29. Psoter WJ, Zhang H, Pendrys DG, Morse DE, Mayne ST (2003) Classification of dental caries patterns in the primary dentition: a multidimensional scaling analysis. Community Dent Oral Epidemiol 31:231–238. doi:10.1034/j.1600-0528.2003.00044.x

    Article  PubMed  Google Scholar 

  30. The World Oral Health Report (2003) Continuous improvement of oral health in the 21st century—the approach of the WHO Global Oral Health Programme, realised by the World Health Organization, 45 pp. Accessed 15 August 2006

  31. Wang X, Shaffer JR, Weyant RJ, Cuenco KT, DeSensi RS, Crout R, McNeil DW, Marazita ML (2010) Genes and their effects on dental caries may differ between primary and permanent dentitions. Caries Res 44:277–284. doi:10.1159/000314676

    Article  PubMed  Google Scholar 

  32. Kurczynski TW, Berns JS, Johnson WE (1982) Studies of a family with incontinentia pigmenti variably expressed in both sexes. J Med Genet 19:447–451

    Article  PubMed  Google Scholar 

  33. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC (2009) Cleft lip and palate. Lancet 374:1773–1785. doi:10.1016/S0140-6736(09)60695-4

    Article  PubMed  Google Scholar 

  34. Minić S, Obradović M, Kovačević I, Trpinac D (2010) Ocular anomalies in Incontinentia pigmenti—literature review and meta-analysis. Srp Arh Celok Lek 138:408–413. doi:10.2298/SARH1008408M

    Article  PubMed  Google Scholar 

  35. Thesleff I (2006) The genetic basis of tooth development and dental defects. Am J Med Genet A 140A:2530–2535. doi:10.1002/ajmg.a.31360

    Article  Google Scholar 

  36. Arte S, Pirinen S (2004) Hypodontia. Orphanet encyclopedia. Accessed May 2004

  37. Kouskoura T, Fragou N, Alexiou M, John N, Sommer L, Graf D, Katsaros C, Mitsiadis TA (2011) The genetic basis of craniofacial and dental abnormalities. Schweiz Monatsschr Zahnmed 121:636–646

    PubMed  Google Scholar 

  38. Jacobsen P (2008) Restorative dentistry. An integrative approach, 2nd edn. Wiley-Blackwell, Oxford

    Google Scholar 

  39. Jensen JL, Album B (2011) Tooth transplantation in cherubism and incontinentia pigmenti: report of two unusual cases. Oral Surg 4:39–43. doi:10.1111/j.1752-248X.2010.01105.x

    Article  Google Scholar 

  40. Ciminello FS, Morin RJ, Nguyen TJ, Wolfe SA (2009) Cleft lip and palate: review. Compr Ther 35:37–43

    PubMed  Google Scholar 

  41. Martinez-Pomar N, Munoz-Saa I, Heine-Suner D, Martin A, Smahi A, Matamoros N (2005) A new mutation in exon 7 of NEMO gene: late skewed X-chromosome inactivation in an incontinentia pigmenti female patient with immunodeficiency. Hum Genet 118:458–465. doi:10.1007/s00439-005-0068-y

    Article  PubMed  Google Scholar 

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Correspondence to Snežana Minić.

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Minić, S., Trpinac, D., Gabriel, H. et al. Dental and oral anomalies in incontinentia pigmenti: a systematic review. Clin Oral Invest 17, 1–8 (2013).

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