title: Familial multiple discoid fibromas: a look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus.
abstract: BACKGROUND
  Previously, we proposed that familial multiple trichodiscomas (OMIM 190340) is distinct from Birt-Hogg-Dubé syndrome (BHD) (OMIM #135150). BHD is characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothorax, and renal cell cancer. Germline FLCN mutations can be detected in most but not all BHD families.
  
  
  OBJECTIVE
  We sought to evaluate familial multiple trichodiscomas at a clinical and genetic level. We now renamed this condition "familial multiple discoid fibromas" (FMDF) to emphasize the distinction from BHD.
  
  
  METHODS
  In 8 additional families with an autosomal dominant pattern of multiple discoid fibromas we assessed the clinical findings and the histopathological features of skin lesions. FLCN germline mutation analysis was completed in 7 families. In two of these families segregation analysis was performed using polymorphic DNA markers in and around the FLCN locus.
  
  
  RESULTS
  The clinical findings in FMDF are different from those in BHD with early onset of skin lesions, prominent involvement of the pinnae, and discoid fibromas without the follicular epithelial component characteristic of the fibrofolliculoma/trichodiscoma spectrum of BHD. In addition, there were no evident pulmonary or renal complications. In none of the families were pathogenic FLCN germline mutations identified. Using segregation analysis we could exclude involvement of the FLCN locus in the two kindreds tested.
  
  
  CONCLUSIONS
  The prevalence of FMDF is presently unknown. The underlying gene defect has not yet been identified.
  
  
  CONCLUSIONS
  FMDF is clinically distinct from BHD and is not linked to the FLCN locus.
authors.affiliation: Birt-Hogg-Dubé Working Group, Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands. thm.starink@vumc.nl
authors.forename: Theo M
authors.initials: TM
authors.lastname: Starink
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Houweling
authors.forename: Martijn B A
authors.initials: MB
authors.lastname: van Doorn
authors.forename: Edward M
authors.initials: EM
authors.lastname: Leter
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Jaspars
authors.forename: R Jeroen A
authors.initials: RJ
authors.lastname: van Moorselaar
authors.forename: Piet E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Paul C
authors.initials: PC
authors.lastname: Johannesma
authors.forename: Jan Hein
authors.initials: JH
authors.lastname: van Waesberghe
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Ploeger
authors.forename: Marieke T
authors.initials: MT
authors.lastname: Kramer
authors.forename: Johan J P
authors.initials: JJ
authors.lastname: Gille
authors.forename: Quinten
authors.initials: Q
authors.lastname: Waisfisz
authors.forename: Fred H
authors.initials: FH
authors.lastname: Menko
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D058249:Birt-Hogg-Dube Syndrome / Q000175:diagnosis* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005350:Fibroma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012878:Skin Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins