Birt-Hogg-Dubé syndrome: an underdiagnosed genetic tumor syndrome

J Dtsch Dermatol Ges. 2018 Mar;16(3):278-283. doi: 10.1111/ddg.13457.

Abstract

Birt-Hogg-Dubé syndrome (BHD, also referred to as Hornstein-Knickenberg syndrome) is an autosomal dominant tumor syndrome caused by mutations in the FLCN gene located on chromosome 17. Depending on their age, patients with BHD may exhibit various clinical signs and symptoms. Disease severity can vary greatly among members of the same family. Early symptoms include basal lung cysts, which can lead to recurrent spontaneous pneumothoraces. The majority of patients (> 90 %) develop multiple fibrofolliculomas, especially on the face and upper trunk, in the second or third decade of life. Given the 12-34 % lifetime risk of developing benign or malignant renal tumors, targeted screening programs are prognostically crucial. While these renal tumors may belong to various histological subtypes, common variants include multifocal - sometimes bilateral - chromophobe and oncocytic hybrid tumors. Early diagnosis and adequate long-term care of families with BHD require interdisciplinary cooperation.

Publication types

  • Review

MeSH terms

  • Birt-Hogg-Dube Syndrome / diagnosis*
  • Birt-Hogg-Dube Syndrome / genetics*
  • Birt-Hogg-Dube Syndrome / therapy
  • Chromosomes, Human, Pair 17 / genetics
  • DNA Mutational Analysis
  • Genes, Dominant / genetics
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / therapy
  • Lung Diseases / diagnosis
  • Lung Diseases / genetics
  • Lung Diseases / therapy
  • Proto-Oncogene Proteins / genetics
  • Rare Diseases* / genetics
  • Skin Diseases / diagnosis
  • Skin Diseases / genetics
  • Skin Diseases / therapy
  • Tumor Suppressor Proteins / genetics

Substances

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