Oral Manifestations of Neurofibromatosis Type 1 in Children with Facial Plexiform Neurofibroma: Report of Three Cases

Neurofibromatosis type 1 (NF1) is a common autosomal genetic disorder with a prevalence of 1 in 3,000 births. NF1 is a complex syndrome characterized by many abnormalities and may affect all organ systems. Oral manifestations of NF1 occur frequently, but reports including NF1 children with facial plexiform neurofibromas and oral alterations are scant. Facial plexiform neurofibroma may cause asymmetry, disfigurement and usually arises from the trigeminal nerve. The aim of this paper is to to report three pediatric NF1 cases with facial plexiform neurofibroma presenting with oral manifestations, which were evaluated clinically and radiographically, and also to briefly review the literature. Patients presented with changes in the oral soft tissues, jaws, and teeth ipsilateral to the tumor.

Neurofibromatosis 1, plexiform neurofibroma, oral manifestations, child

1. Friedman JM and Birch PH. Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients. Am J Med Genet 70: 138–143, 1997.

2. Huson SM, Compston DA, Clark P and Harper PS. A genetic study of von Recklinghausen neurofibromatosis in South East Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 26: 704–711, 1989.

3. Takano T, Kawashima T, Yamanouchi Y, Kitayama K, Baba T, Ueno K et al. Genetics of neurofibromatosis 1 in Japan: mutation rate and paternal age effect. Hum Genet 89: 281–286, 1992.

4. Young H, Hyman S, and North K. Neurofibromatosis 1: clinical review and exceptions to the rules. J Child Neurol 17: 613–621, 2002.

5. Shapiro SD, Abramovitch K, Van Dis ML, Skoczylas LJ, Langlais RP, Jorgenson RJ et al. Neurofibromatosis: oral and radiographic manifestations. Oral Surg Oral Med Oral Pathol 58: 493–498, 1984.

6. D’Ambrosio JA, Langlais RP and Young RS. Jaw and skull changes in neurofibromatosis. Oral Surg Oral Med Oral Pathol 66: 391–396, 1988.

7. Friedrich RE, Giese M, Schmelzle R, Mautner VF and Scheuer HA. Jaw malformations plus displacement and numerical aberrations of teeth in neurofibromatosis type 1: a descriptive analysis of 48 patients based on panoramic radiographs and oral findings. J Craniomaxillofac Surg 31: 1–9, 2003.

8. Visnapuu V, Peltonen S, Tammisalo T, Peltonen J and Happonen RP. Radiographic findings in the jaws of patients with Neurofibromatosis 1. J Oral Maxillofac Surg 70: 1351-1357, 2012.

9. Sigillo R, Rivera H, Nikitakis NG and Sauk JJ. Neurofibromatosis type 1: a clinicopathological study of the orofacial manifestations in 6 pediatric patients. Pediatr Dent 24: 575–580, 2002.

10. Stumpf DA, Alksne JF, Annegers JF, Brown SS, Conneally PM, Housman D et al. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol 45, 1998.

11. Cunha KS, Barboza EP, Da Fonseca EC. Identification of growth hormone receptor in localised neurofibromas of patients with neurofibromatosis type 1. J Clin Pathol 56: 758–63, 2003.

12. Geller M, Mezitis SG, Nunes FP, Ribeiro MG, Araújo AP, Bronstein MD et al. Progesterone and Estrogen Receptors in Neurofibromas of Patients with NF1. Clin Med Pathol 1: 93–97, 2008.

13. Cunha KSG and Geller M. Advances in Neurofibromatosis Research. Ed. Nova Science Publishers Inc, New York; 25–41, 2012.

14. Waggoner DJ, Towbin J, Gottesman G and Gutmann DH. Clinic-based study of plexiform neurofibromas in neurofibromatosis 1. Am J Med Genet 92: 132–135, 2000.

15. Korf BR. Plexiform neurofibromas. Am J Med Genet 89: 31–37, 1999.

16. Korf BR. Neurofibromas and malignant tumors of the peripheral nerve sheath. Friedman JM, Gutmann DH, MacCollin M. In: Neurofibromatosis: Phenotype, Natural History, and Pathogenesis. Ed. The Johns Hopkins University Press, Baltimore; 142–161, 1999.

17. Overdiek A, Feifel H, Schaper J, Mayatepek E and Rosenbaum T. Diagnostic delay of NF1 in hemifacial hypertrophy due to plexiform neurofibromas. Brain Dev 28: 275–280, 2006.

18. Güneri EA, Akoglu E, Sütay S, Ceryan K, Sagol O and Pabuçcuoglu U. Plexiform neurofibroma of the tongue: a case report of a child. Turk J Pediatr 48: 155–158, 2006.

19. Sharma SC and Srinivasan S. Isolated plexiform neurofibroma of tongue and oropharynx: a rare manifestation of von Recklinghausen’s disease. J Otolaryngol 27: 81–84, 1998.

20. Fadda MT, Verdino G, Mustazza MC, Bartoli D and Iannetti G. Intra-parotid facial nerve multiple plexiform neurofibroma in patient with NF1. Int J Pediatr Otorhinolaryngol 72: 553–557, 2008.

21. Thammaiah S, Manjunath M, Rao K and Uma DHS. Intraoral plexiform neurofibroma involving the maxilla - pathognomonic of neurofibromatosis type I. J Pediatric Neuroscience 6: 65–68, 2011.

22. Friedrich RE, Giese M, Stelljes C, Froeder C and Scheuer HA. Size of tooth crowns and position of teeth concerning the extension of facial plexiform neurofibroma in patients with neurofibromatosis type 1. Anticancer Res 32: 2207–2214, 2012.

23. Bardellini E, Amadori F, Flocchini P, Conti G, Plana G and Majorana A. Oral findings in 50 children with neurofibromatosis type 1. A case control study. Eur J Pediatric Dent 12, 256–260, 2011.

24. Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM and Ilstrup DM. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 57: 2006–2021, 1986.