Familial spontaneous pneumothorax

Curr Opin Pulm Med. 2006 Jul;12(4):268-72. doi: 10.1097/01.mcp.0000230630.73139.f0.


Purpose of review: Over 10% of patients with primary spontaneous pneumothorax report a positive family history of the disease. While some cases can be attributed to rare inherited connective tissue diseases, several families with familial spontaneous pneumothorax have been described that do not show clinical evidence of these monogenic disorders. Until recently the molecular underpinning of this disease was unknown.

Recent findings: In the last 18 months, mutations in the gene encoding folliculin (FLCN) have been identified in individuals with familial spontaneous pneumothorax. Mutations in this gene were known previously to cause a rare skin disease, Birt-Hogg-Dubé syndrome, an autosomal dominantly inherited disease characterized by benign skin tumors, diverse types of renal cancer, pulmonary cysts, and spontaneous pneumothorax. Two animal models and studies of renal cancers support a tumor-suppressor function for folliculin. The presence of thin-walled cysts in basilar and subpleural locations of the lung is a feature of this disease. Most families display reduced penetrance of the pneumothorax phenotype. Several individuals with a family history of spontaneous pneumothorax have a mutation in the folliculin gene.

Summary: A significant fraction of families with familial spontaneous pneumothorax have mutations in the folliculin gene and should be considered a forme fruste of Birt-Hogg-Dubé syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Humans
  • Mutation / genetics
  • Pneumothorax / genetics*
  • Proteins / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Tumor Suppressor Proteins / genetics*


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