Genetic and Dental Study of Patients with Celiac Disease

The aim of this work was to study the pattern of inheritance of celiac disease in a group of Saudi patients and to compare oral mucosal and dental clinical findings in these patients to those of healthy controls. Study design: Fifty patients suffering from celiac disease were screened for dental evaluation. They were subjected to clinical genetic examination, pedigree construction, oral mucosal and dental clinical evaluation. Results: An autosomal recessive mode of inheritance was evident in some of the studied cases, while others showed sporadic occurrence. Oral mucosal and dental clinical examinations revealed recurrent oral ulcerations, enamel hypoplasia in most of the celiac disease patients. Conclusions: Pedigree analysis of families is important to identify the mode of inheritance. Oral mucosal and dental clinical examinations are important in diagnosing and monitoring cases of celiac disease.

genetic and dental study, patients, celiac disease

1. Koning F, Schuppan D, Cerf-Bensussan N, Sollid LM. Pathomechanisms in celiac disease. Best Pract Res Clin Gastroenterol, 19: 373–387, 2005.

2. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med, 163: 286–292, 2003.

3. Sollid LM. Molecular basis of celiac disease. Annu Rev Immunol, 18: 53–81, 2000.

4. Ellis A: Coeliac disease: family and twin studies and disease associations, in ibid.

5. Strober W: Gluten-sensitive enteropathy. Clin Gastroenterol, 5: 429–450, 1976.

6. Book L, Zone JJ, Neuhausen SL. Prevalence of celiac disease among relatives of sib pairs with celiac disease in US families. Am J Gastroenterol, 98: 377–381, 2003.

7 Houlston RS, Ford D. Genetics of coeliac disease. QJM, 89: 737–743, 1996.

8. Korponay-Szabo I, Kovacs J, Lorincz M, Torok E, Goracz G. Families with multiple cases of gluten-sensitive enteropathy. Z Gastroenterol, 36: 553–558, 1998.

9. Trier JS. Celiac sprue. N Engl J Med, 325: 1709–1719, 1991.

10. Spurkland A, Ingvarsson G, Falk ES, Knutsen I, Sollid LM, Thorsby E. Dermatitis herpetiformis and celiac disease are both primarily associated with the hla-dq (alpha 1*0501, beta 1*02) or the hla-dq (alpha 1*03, beta 1*0302) heterodimers. Tissue Antigens, 49: 29–34, 1997.

11. Bevan S, Popat S, Braegger CP, Busch A, O’Donoghue D, Falth-Magnusson K, et al. Contribution of the mhc region to the familial risk of coeliac disease. J Med Genet, 36: 687–690, 1999.

12. Lewis C, Book L, Black J, Sawitzke A, Cannon-Albright L, Zone J, et al. Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in self-diagnosed individuals, dosage effect, and sibling risk. J Pediatr Gastroenterol Nutr, 31: 22–27, 2000.

13. Petronzelli F, Bonamico M, Ferrante P, Grillo R, Mora B, Mariani P, et al. Genetic contribution of the hla region to the familial clustering of coeliac disease. Ann Hum Genet, 61: 307–317, 1997.

14. Risch N. Assessing the role of hla-linked and unlinked determinants of disease. Am J Hum Genet, 40: 1–14, 1987.

15. Collin P, Reunala T, Pukkala E, et al. Coeliac disease-associated diseases and survival. Gut, 35: 1215–1218, 1994.

16. Corazza GR, Di Sario A, Ceccetti L, et al. Bone mass and metabolism in patients with celiac disease. Gastroenterology, 109: 122–128, 1995.

17. Collin P, Reunala T, Rasmussen M, et al. High incidence and prevalence of adult celiac disease. Augmented diagnostic approach. Scand J Gastroenterol, 32: 1129–1133, 1997.

18. Aine L, Mäki M, Collin P, et al. Dental enamel defects in celiac disease. J Oral Pathol Med, 19: 241–245, 1990.

19. Aquirre JM, Rodriquez R, Oribe D, et al. Dental enamel defects in celiac patients. Oral Surg Oral Med Oral Patholo Oral Radiol Endod, 84: 646–650, 1997.

20. Lähteenoja H, Toivanen A, Viander M, Maki M, Irjala K, Syrjanen S. Oral mucosa changes in celiac patients on a gluten-free diet. Eur J Oral Sci, 105: 899–906, 1998.

21. Patinen P, Aine L, Collin P; Hietanen J, Korpela M, Enckell G, Kautianinen H, Konttinen YT, Reunala T. Oral findings in coeliac disease and Sjogren’s symdrome. Oral Dis, 10 (6): 330–334, 2004.

22. Accomando S, Cataldo F. The global village of celiac disease. Dig Liver Dis, 36(7): 492–498, 2004.

23. Pastore L, De Benedittis M, Petruzzi M, Tato D, Napoli C, Montagna MT, Catassi C, Serpico R. Importance of oral signs in the diagnosis of atypical forms of celiac disease. Recenti Prog Med, 95: 482–490, 2004.

24. Carroccio A, Iannitto E, Cavataio F, Montalto G, Tumminello M, Campagna P, Lipari MG, Notarbartolo A, Iacono G. Sideropenic anemia and celiac disease: one study, two points of view. Dig Dis Sci, 43(3): 673–678, 1998.

25. Vader W, Stepniak D, Kooy Y, Mearin L, Thompsont A, van Rood JJ, Spaenij L, Koning F. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. PNAS, 100(21): 12390–12395, 2003.

26. Cronin CC, Feighery A, Ferriss B, Liddy C, Shanahan F, Feighery C. High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus. Am. J. Gastroenterol, 92: 2210–2212, 1997.

27. Saukkonen T, Savilahti E, Reijonen H, Honen J, Tuomilehto-Wolf E, Akerblom HK. Coeliac disease: frequent occurrence after clinical onset of insulin dependent diabetes mellitus. Childhood Diabetes in Finland Study Group. Diabetes Med, 13: 464–470, 1996.

28. Strober W. Genetic factors in gluten-sensitive enteropathy, in Genetics and Heterogeneity of common gastrointestinal disorders, edited by Rotter JI, Samloff IM, Rimoin DL, New York, Academic Press, pp 243–259, 1980.

29. Polanco I, Biemond I, Leeuwen A. Gluten sensitive enteropathy in Spain: genetic and environmental factors. In: McConnell RB, ed. The genetics of celiac disease. Lancaster: MTP Press, 211–230, 1981.

30. Megiorni F, Mora B, Bonamico M, Barbato M, Montuori M, Viola F, Trabace S, Mazzilli MC. HLA-DQ and susceptibility to celiac disease:evidence for gender difference and parent-of-origin effects. Am J Gastroenterol, 103(4): 997–1003, 2008.

31. Thorsby E and Rønningen KS. Particular HLA-DQ molecules play a dominant role in determining susceptibility or resistance to Type 1 (insulin-dependent) diabetes mellitus. Diabetologia, 36: 371, 1993.

32. Elfstrome P, Montgomery SM, Kampe O, Ekbom A, Ludvigsson JF. Risk of thyroid disease in individuals with Celiac disease. L Clin Endocrinol Metab 2008 (in press).

33. Takeda R, Takayama Y, Tagawa S, Kornel L. Schmidt’s syndrome: autoimmune polyglandular disease of the adrenal and thyroid glands. Isr Med Assoc J, 1:285–286, 1999.

34. Greenberg DA, Rotter JI. Two-locus models: for gluten sensitive enteropathy: population genetic considerations. Am J Med Genet, 8: 205–214, 1981.

35. Nelson. Essentials of Pediatrics. 5th ed. Elsevier Saunders. Philadelphia, PA, USA, 2006.

36. Petrecca S, Giammaria G, Giammaria AF. Oral cavity changes in the child with celiac disease. Minerva Stomatol, 43(4): 137–140, 1994.

37. Dewar D, Pereira SP, Ciclitira PJ. The pathogenesis of coeliac disease. Int J Biochem Cell Bio, 36(1): 17–24, 2004.

38. Catassi C, Fabiani E, Corrao G, Barbato M, De Renzo A, et al. Risk of non-Hodgkin lymphoma in celiac disease. JAMA, 287: 1413–1419, 2002.

39. Sedghizadeh PP, Shuler CF, Allen CM, Beck FM, Kalmar JR. Celiac disease and recurrent aphthous stomatitis: a report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 94: 474–478, 2002.

40. Rasmusson CG, Eriksson MA. Celiac disease and mineralisation disturbances of permanent teeth. Int J Paediatr Dent, 11: 179–183, 2001.

41. Aine L. Dental enamel defects and dental maturity in children and adolescents with coeliac disease. Proc Finn Dent Soc, 82 Suppl 3: 1–71, 1986.

42. Economopoulou P, Laskaris G. Dermatitis herpetiformis: oral lesions as an early manifestation. Oral Surg Oral Med Oral Pathol, 62: 77–80, 1986.

43. Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology, 117: 297–303, 1999.

44. Iltanen S, Collin P, Korpela M, Holm K, Partanen J, Polvi A, Maki M. Celiac disease and markers of celiac disease latency in patients with primary Sjogren’s syndrome. Am J Gastroenterol, 94: 1042–1046, 1999.

45. Scully C, Porter SR, Eveson JW. Oral lichen planus and coeliac disease. Lancet, 341: 1660, 1993.

46. Bhatnagar S, Tandon N. Diagnosis of celiac disease. Indian J Pediatr, 73: 703–709, 2006.

47. Finizio M, Quaremba G, Mazzacca G, Ciacci C. Large forehead: a novel sign of undiagnosed coeliac disease. Dig Liver Dis, 37(9): 659–664, 2005.

48. Farmakis E, Puntis JW, Toumba KJ. Enamel defects in children with coeliac disease. Eur J Paediatr Dent, 6(3): 129–132, 2005.

49. Wortsman J and Kumar V. Idiopathic hypoparathyroidism co-existing with celiac disease: immunologic studies. Am J Med Sci, 307: 420–427, 1994.

50. Ojetti V, Nucera G, Migneco A, Gabrielli M, Lauritano C, Danese S, Zocco MA, Nista EC, Cammarota G, De Lorenzo A, Gasbarrini G, Gasbarrini A. Higher prevalence of celiac disease in patients with lactose intolerance. Digestion, 71(2): 106–110, 2005.

51. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc, 134: 200–207, 2003.

52. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med, 9: 306–321, 1998.

53. Jurge S, Kuffer R, Scully C, Porter SR. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis, 12(1): 1–21, 2006