A vestibular schwannoma in a patient with Birt-Hogg-Dube syndrome

Genet Couns. 2014;25(2):203-8.

Abstract

Birt-Hogg Dubé syndrome is an autosomal dominant disease with variable clinical expression. It is characterized by cutaneous manifestations, renal tumors and lung cysts. Other tumors, such as adrenal tumors and tumors originating from the neural crest cells such as meningioma and neurothekeoma have also been described. This syndrome is caused by germline mutations in the folliculin (FLCN) gene located on chromosome 17p. We report, for the first time, a patient with BHDS and a history of a vestibular schwannoma in adolescence. The diagnosis of BHDS was confirmed, by identifying a nonsense mutation in exon 10 of the FLCN gene. A vestibular schwannoma also originates from neural crest cells, just as other neural tumors, previously encountered in patients with BHDS. The reported mutations cause a truncation of the protein, folliculin. The exact role of folliculin is still undetermined. Two different theories suggest the effect of tumorigenesis. One is that folliculin plays an important role in the AMPK-mTOR pathway which leads to proliferation of cells when activated. The other is that the folliculin acts as a possible tumor suppressor gene, since there is a high frequency of second hits in the FLCN-gene. In order to confirm a possible relation of BHDS and neural crest tumors, further research is necessary in the tumorigenesis of the folliculin gene.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Birt-Hogg-Dube Syndrome / complications
  • Birt-Hogg-Dube Syndrome / genetics*
  • Codon, Nonsense
  • Exons / genetics
  • Female
  • Humans
  • Neuroma, Acoustic / etiology*
  • Neuroma, Acoustic / surgery
  • Proto-Oncogene Proteins / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Codon, Nonsense
  • FLCN protein, human
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins