The Relevance of Family History Taking in the Detection and Management of Birt-Hogg-Dubé Syndrome

Respiration. 2019;98(2):125-132. doi: 10.1159/000498973. Epub 2019 Jul 2.


Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant inherited disorder characterized by inactivation of the gene Folliculin (FLCN), pulmonary cysts with recurrent spontaneous pneumothorax, dermatological lesions, and an increased risk of developing renal malignancies.

Objectives: We aimed to investigate the real prevalence of BHDS and its prevalence among patients with a familial history of pneumothorax.

Methods: From July 2014 to December 2016, we consecutively studied all patients with spontaneous pneumothorax and a positive family history for the same condition referring to our Institution. The suspicious cases underwent genetic analysis of the BHDS-causative gene FLCN. FLCN-positive cases were further evaluated with routine blood tests, chest radiography, chest CT, abdominal MRI, and dermatological evaluation.

Results: Among 114 patients admitted with spontaneous pneumothorax, 7 patients had a family history of pneumothorax, and 6/7 (85.7%) patients had positive genetic test for FLCN as well as 7/13 family members. Pulmonary cysts were found in all patients with a FLCN-positive genetic test. Most patients (10/13, 76.9%) had tiny pulmonary cysts less than 1 cm in diameter. The vast majority of cysts were intraparenchymal (12/13, 92.3%) and located in lower lobes. Dermatological lesions were found in 7/13 (54%) patients, renal cysts in 4/13 (31%) patients, and renal cancer in 1 (1/13, 7.7%) patient.

Conclusions: Although BHDS is considered a rare disease, BHDS underlies spontaneous pneumothorax more often than usually believed, especially whenever a family history of pneumothorax is present. Diagnosis of BHDS is essential to start monitoring patients for the risk of developing renal malignancies.

Keywords: Birt-Hogg-Dubé syndrome; Computed tomography; Cysts; FLCN protein; Pneumothorax; Prevalence; Radiography; Rare diseases.

MeSH terms

  • Adult
  • Aged
  • Birt-Hogg-Dube Syndrome / diagnosis*
  • Birt-Hogg-Dube Syndrome / epidemiology
  • Birt-Hogg-Dube Syndrome / genetics
  • Cysts / diagnostic imaging
  • Female
  • Genetic Testing
  • Humans
  • Kidney Diseases, Cystic / diagnostic imaging
  • Lung Diseases / diagnostic imaging
  • Male
  • Medical History Taking*
  • Middle Aged
  • Pneumothorax / genetics*
  • Prevalence
  • Proto-Oncogene Proteins / genetics*
  • Tumor Suppressor Proteins / genetics*


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