The Genetics of Pneumothorax

Am J Respir Crit Care Med. 2019 Jun 1;199(11):1344-1357. doi: 10.1164/rccm.201807-1212CI.


A genetic influence on spontaneous pneumothoraces-those occurring without a traumatic or iatrogenic cause-is supported by several lines of evidence: 1) pneumothorax can cluster in families (i.e., familial spontaneous pneumothorax), 2) mutations in the FLCN gene have been found in both familial and sporadic cases, and 3) pneumothorax is a known complication of several genetic syndromes. Herein, we review known genetic contributions to both sporadic and familial pneumothorax. We summarize the pneumothorax-associated genetic syndromes, including Birt-Hogg-Dubé syndrome, Marfan syndrome, vascular (type IV) Ehlers-Danlos syndrome, alpha-1 antitrypsin deficiency, tuberous sclerosis complex/lymphangioleiomyomatosis, Loeys-Dietz syndrome, cystic fibrosis, homocystinuria, and cutis laxa, among others. At times, pneumothorax is their herald manifestation. These syndromes have serious potential extrapulmonary complications (e.g., malignant renal tumors in Birt-Hogg-Dubé syndrome), and surveillance and/or treatment is available for most disorders; thus, establishing a diagnosis is critical. To facilitate this, we provide an algorithm to guide the clinician in discerning which cases of spontaneous pneumothorax may have a genetic or familial contribution, which cases warrant genetic testing, and which cases should prompt an evaluation by a geneticist.

Keywords: gene; Birt-Hogg-Dubé syndrome; familial spontaneous pneumothorax; genetics; pneumothorax.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Birt-Hogg-Dube Syndrome / genetics*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Mutation
  • Pedigree
  • Pneumothorax / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Tumor Suppressor Proteins / genetics*


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