Age-dependent oral manifestations of neurofibromatosis type 1: a case–control study

Eshwar Thota, John Jims Veeravalli, Sai Krishna Manchala, Bhargavi Priya Lakkepuram, Jayasurya Kodapaneni, Yi Wen Chen, Li Tzu Wang, Kevin Sheng Kai Ma

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Introduction: Most craniofacial manifestations of neurofibromatosis type 1 (NF1) are considered as a result of tumor compression. We sought to determine salivary changes, caries, and periodontal complications in NF1 patients without tumors in the oral cavity. Objective and methods: Eleven NF1 patients without tumors in the oral cavity and 29 matched controls without NF1 were enrolled in this case–control study. Demographic information, medical history, and data of intraoral examinations, including the Decayed, Missing, and Filled Teeth (DMFT) scores and Russel’s periodontal index (PI), were recorded. The functional salivary analysis was performed for sialometry, salivary pH values, and amylase activity. Ingenuity Systems Pathway Analysis (IPA) was conducted to identify mutually activated pathways for NF1-associated oral complications. Results: NF1 patients were associated with periodontitis (OR = 1.40, 95% CI = 1.06–1.73, P = 0.04), gingivitis (OR = 1.55, 95% CI = 1.09–2.01, P = 0.0002), and decreased salivary flow rates (OR = 1.40, 95% CI = 1.05–1.76, P = 0.005). Periodontal destruction, salivary changes, and dental caries in NF1 patients were age-dependent. Subgroup analyses based on age stratification suggested that salivary flow rates and salivary amylase activities were significantly low in NF1 patients aged over 20 years and that salivary pH values, PI and DMFT scores were significantly high among NF1- controls aged over 20. All oral complications were not significantly presented in NF1 patients aged below 20 years. IPA analyses suggested that cellular mechanisms underlying NF1-associated oral complications involved chronic inflammatory pathways and fibrosis signaling pathway. Conclusion: NF1 patients without tumors in the oral cavity presented a comparatively high prevalence of age-dependent oral complications, including periodontal destruction and salivary gland dysfunction, which were associated with chronic inflammatory pathogenesis.

Original languageEnglish
Article number93
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - Dec 2022
Externally publishedYes


  • Dental caries
  • Neurofibromatosis type 1
  • Oral complications
  • Periodontitis
  • Salivary gland dysfunction

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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