The Genetics of Pneumothorax

• Published in: American journal of respiratory and critical care medicine Vol. 199; no. 11; pp. 1344 - 1357
• Main Authors: Boone, Philip M., Scott, Rachel M., Marciniak, Stefan J., Henske, Elizabeth P., Raby, Benjamin A.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.06.2019
• Subjects: Birt-Hogg-Dube Syndrome - genetics; Concise Clinical Review; Cystic fibrosis; Cysts; Family medical history; Genes; Genetic Predisposition to Disease; Genetic Testing; Genetics; Genotype & phenotype; Hospitals; Humans; Lung diseases; Marfan syndrome; Medicine; Mutation; Pedigree; Pneumothorax - genetics; Proto-Oncogene Proteins - genetics; Tomography; Tumor Suppressor Proteins - genetics; United Kingdom > UK; Massachusetts; familial spontaneous pneumothorax; genetics; gene; Birt-Hogg-Dubé syndrome; pneumothorax
• ISSN: 1073-449X; 1535-4970; 1535-4970
• 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: ) pneumothorax can cluster in families (i.e., familial spontaneous pneumothorax), ) mutations in the gene have been found in both familial and sporadic cases, and ) 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.