Making extra teeth: Lessons from a TRPS1 mutation

Am J Med Genet A. 2017 Jan;173(1):99-107. doi: 10.1002/ajmg.a.37967. Epub 2016 Oct 5.


A Thai mother and her two daughters were affected with tricho-rhino-phalangeal syndrome type I. The daughters had 15 and 18 supernumerary teeth, respectively. The mother had normal dentition. Mutation analysis of TRPS1 showed a novel heterozygous c.3809_3811delACTinsCATGTTGTG mutation in all. This mutation is predicted to cause amino acid changes in the Ikaros-like zinc finger domain near the C-terminal end of TRPS1, which is important for repressive protein function. The results of our study and the comprehensive review of the literature show that pathways of forming supernumerary teeth appear to involve APC and RUNX2, the genes responsible for familial adenomatous polyposis syndrome and cleidocranial dysplasia, respectively. The final pathway resulting in supernumerary teeth seems to involve Wnt, a morphogen active during many stages of development. © 2016 Wiley Periodicals, Inc.

Keywords: Langer-Giedion syndrome; Wnt signaling; exostosis; extra teeth; supernumerary teeth; tricho-rhino-phalangeal syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Facies
  • Female
  • Fingers / abnormalities
  • Fingers / surgery
  • Genetic Association Studies
  • Hair Diseases / diagnosis
  • Hair Diseases / genetics
  • Hair Diseases / surgery
  • Heterozygote
  • Humans
  • Langer-Giedion Syndrome / diagnosis
  • Langer-Giedion Syndrome / genetics
  • Langer-Giedion Syndrome / surgery
  • Middle Aged
  • Models, Biological
  • Mutation*
  • Nose / abnormalities
  • Nose / surgery
  • Phenotype
  • Radiography
  • Repressor Proteins
  • Tooth, Supernumerary / diagnosis*
  • Tooth, Supernumerary / genetics*
  • Tooth, Supernumerary / surgery
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Repressor Proteins
  • TRPS1 protein, human
  • Transcription Factors

Supplementary concepts

  • Trichorhinophalangeal Syndrome, Type I