Atypical Orofacial Conditions in Noonan Syndrome: A Case Report

Noonan syndrome (NS) is a relatively common condition characterized by chest deformation, congenital heart disease, short stature and distinctive facial features. Due to its genetic heterogeneity NS patients exhibit a range of clinical signs. Severe gingivitis and supernumerary teeth are rarely seen in connection with NS. In addition, there has not been a report on NS patients with atypical bilateral enlargement of the mental foramens and inferior-alveolar canals. This case report describes a NS patient who has undergone growth hormone (GH) therapy and is presenting with classical and rare NS phenotypes.

Noonan syndrome (NS), growth hormone (GH), supernumerary teeth

1. Noonan JA. Noonan syndrome and related disorders: alterations in growth and puberty. Rev Endocr Metab Disord, 7: 251–255, 2006.

2. Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics, 126: 746–759, 2010.

3. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kre-mer H, et al. Mutations in PTPN11, encoding the protein tyrosine phos-phatase SHP-2, cause Noonan syndrome. Nat Genet, 29: 465–468, 2001.

4. Schubbert S, Zenker M, Rowe SL, Böll S, Klein C, Bollag G, et al. Germline KRAS mutations cause Noonan syndrome. Nat Genet, 38: 331–336, 2006.

5. Carta C, Pantaleoni F, Bocchinfuso G, Stella L, Vasta I, Sarkozy A, et al. Germline missense mutations affecting KRAS isoform B are asso-ciated with a severe Noonan syndrome phenotype. Am J Hum Genet, 79: 129–135, 2006.

6. Cirstea IC, Kutsche K, Dvorsky R, Gremer L, Carta C, Horn D, et al. A restricted spectrum of NRAS mutations cause Noonan syndrome. Nat Genet, 42: 27–29, 2010.

7. Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet, 39: 70–74, 2007.

8. Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet, 39: 1007–1012, 2007.

9. Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, et al. Germline gain-of-function mutations in RAF1 cause Noonan syn-drome. Nat Genet, 39: 1013–1017, 2007.

10. Sarkozy A, Carta C, Moretti S, Zampino G, Digilio MC, Pantaleoni F, et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofa-ciocutaneous syndromes: molecular diversity and associated pheno-typic spectrum. Hum Mutat, 30: 695–702, 2009.

11. Cordeddu V, Di Schiavi E, Pennacchio LA, Ma’ayan A, Sarkozy A, Fodale V, et al. Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair. Nat Genet, 41: 1022–1026, 2009.

12. Greulich W, Pyle S. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 1st ed. Palo Alto, CA; 1999.

13. 2 to 20 years: Boys Stature-for-age and Weight-for-age percentiles. Atlanta, GA: Centers for Disease Control; 2000. “http://www.cdc.gov/growthcharts/data/set1clinical/cj41c021.pdf”. Accessed November 21, 2010.

14. Collins E, Turner G. The Noonan syndrome: a review of the clinical and genetic features in 27 cases. J Pediatr 83: 941–950, 1973.

15. Horowitz SL, Morishima A. Palatal abnormalities in the syndrome of gonadal dysgenesis and its variants and in Noonan syndrome. Oral Surg, 38: 839–844, 1974.

16. Wilroy RS Jr, Summitt RL, Tipton RE, Primm PA, Martens PR. Phe-notypic heterogeneity in the Noonan syndrome. Birth Defects, 15: 305–311, 1979.

17. Okada M, Sasaki N, Kaihara Y, Okada R, Amano H, Miura K, Kozai K. Oral findings in Noonan syndrome: report of a case. J Oral Sci, 45: 117–121, 2003.

18. Asokan S, Muthu MS, Rathna Prabhu V. Noonan syndrome: a case report. J Indian Soc Pedod Prev Dent, 25: 144–147, 2007.

19. Sugar A, Ezsias A, Bloom AL, Morcos WE. Orthognathic surgery in a patient with Noonan syndrome. J Oral Maxillofac Surg, 52: 421–425, 1994.

20. Leache EB, Saavedra Ontiveros D, Maroto Edo M. Etiopathogenic analysis of the caries on three patients with Noonan Syndrome. Med Oral, 8: 136–142, 2003.

21. Emral ME, Akcam MO. Noonan syndrome: a case report. J Oral Sci, 51: 301–306, 2009.

22. Ortega Ade O, Guaré Rde O, Kawaji NS, Ciamponi AL. Orofacial aspects in Noonan syndrome: 2 case report. J Dent Child, 75: 85–90, 2008.

23. Lima DF, Montenegro RM Jr, Vieira AP, Albano MF, Rego DM. Absence of periodontitis in acromegalic patients. Clin Oral Investig, 13: 165–169, 2009.

24. Buduneli N, Alpoz AR, Candan U, Kardesler L, Yetkiner E. Dental management of isolated growth hormone deficiency: a case report. J Clin Pediatr Dent, 29: 263–266, 2005.

25. Wagaiyu EG, Ashley FP. Mouthbreathing, lip seal and upper lip cover-age and their relationship with gingival inflammation in 11-14 year-old schoolchildren. J Clin Periodontol, 18: 698–702, 1991.

26. Gulati MS, Grewal N, Kaur A. A comparative study of effects of mouth breathing and normal breathing on gingival health in children. J Indian Soc Pedod Prev Dent, 16: 72–83, 1998.

27. Tooth IQ. Supernumerary tooth. URL:http://www.toothiq.com/dental-glossary/dental-definition-supernumerary-tooth.html. (Archived by WebCite® at http://www.webcitation.org/5uW55SxoA). Acccessed Nov. 25, 2010.

28. Rajab LD, Hamdan MA. Supernumerary teeth: review of the literature and a survey of 152 cases. Int J Paediatr Dent, 12: 244–254, 2002.

29. Gershenson A, Nathan H, Luchansky E. Mental foramen and mental nerve: changes with age. Acta Anat (Basel), 126: 21–28, 1986.

30. Doskocil M. Mechanism of the reduction of Meckel’s cartilage in man. Folia Morphol (Praha), 37: 113–118, 1989.

31. Thiel C, Wilken M, Zenker M, Sticht H, Fahsold R, Gusek-Schneider GC, Rauch A. Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. Am J Med Genet, 149A: 1263–1267, 2009.

32. Lee L, Yan YH, Pharoah MJ. Radiographic features of the mandible in neurofibromatosis: a report of 10 cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 81: 361–367, 1996.

33. Shapiro SD, Abramovitch K, Van Dis ML, Skoczylas LJ, Langlais RP, Jorgenson RJ, et al. Neurofibromatosis: oral and radiographic manifes-tations. Oral Surg, 58: 493–498, 1984.

34. Nyström AM, Ekvall S, Allanson J, Edeby C, Elinder M, Holmström G, et al. Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1. Clin Genet, 76: 524–534, 2009.

35. Sharland M, Patton MA, Talbot S, Chitolie A, Bevan DH. Coagulation-factor deficiencies and abnormal bleeding in Noonan syndrome. Lancet, 339: 19–21, 1992.

36. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levi-son M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Inter-disciplinary Working Group. J Am Dent Assoc, 139(Suppl): 3S–24S, 2008.

37. Ranke MB. Noonan syndrome: growth to growth hormone - the expe-rience of observational studies. Horm Res, 72(Suppl 2): 36S–40S, 2009.

38. Westphal O. Growth hormone therapy in Noonan syndrome: growth response and characteristics. Horm Res, 72(Suppl 2): 41S–45S, 2009.

39. Dahlgren J. GH therapy in Noonan syndrome: Review of final height data. Horm Res, 72(Suppl 2): 46S–48S, 2009.

40. Otten BJ, Noordam C. Growth in Noonan syndrome. Horm Res, 72(Suppl 2): 31S–35S, 2009.

41. Hwang CJ, Cha JY. Orthodontic treatment with growth hormone ther-apy in a girl of short stature. Am J Orthod Dentofacial Orthop, 126: 118–126, 2004.

42. Hass AD, Simmons KE, Davenport ML, Proffit WR. The effect of growth hormone on craniofacial growth and dental maturation in Turner syndrome. Angle Orthod, 71: 50–59, 2001.

43. Kjellberg H, Wikland KA. A longitudinal study of craniofacial growth in idiopathic short stature and growth hormone-deficient boys treated with growth hormone. Eur J Orthod, 29: 243–250, 2007.

44. Horowitz SL, Morishima A. Palatal abnormalities in the syndrome of gonadal dysgenesis and its variants and in Noonan’s syndrome. Oral Surg Oral Med Oral Pathol, 38: 839–844, 1974.

45. Nelson JF, Tsaknis PJ, Konzelman JL. Noonan’s syndrome: report of a case with oral findings. J Oral Med, 33: 94–96, 1978.

46. Dunlap C, Neville B, Vickers RA, O’Neil D, Barker B. The Noonan syndrome/cherubism association. Oral Surg Oral Med Oral Pathol, 67: 698–705, 1989.

47. Levine B, Skope L, Parker R. Cherubism in a patient with Noonan syn-drome: report of a case. J Oral Maxillofac Surg, 49: 1014–1018, 1991.

48. Addante RR, Breen GH. Cherubism in a patient with Noonan’s syn-drome. J Oral Maxillofac Surg, 54: 210–203, 1996.

49. Nirmal T, Muthu MS, Arranganal P. Noonan syndrome: a case report. J Indian Soc Pedod Prev Dent, 19: 77–79, 2001.

50. Sharma PR, MacFadyen UM, Fung DE. Dental management of a child patient with Noonan’s syndrome. Dent Update, 34: 117–120, 2007.

51. Ierardo G, Luzzi V, Panetta F, Sfasciotti GL, Polimeni A. Noonan syn-drome: A case report. Eur J Paediatr Dent, 11: 97–100, 2010.

52. Bufalino A, Carrera M, Carlos R, Coletta RD. Giant cell lesions in Noonan syndrome: case report and review of the literature. Head Neck Pathol, 4: 174–177, 2010.