Familial Spontaneous Pneumothorax

Hsienchang Thomas Chiu; Christine Kim Garcia


Curr Opin Pulm Med. 2006;12(4):268-272. 

In This Article

Abstract and Introduction

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.

A primary spontaneous pneumothorax occurs when air collects in the pleural space without preceding trauma in a healthy individual, and without obvious underlying lung disease. It typically occurs in patients between 18 and 40 years of age, whereas a secondary pneumothorax usually occurs in older patients with lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis, pyogenic infections, pulmonary fibrosis and cancer. The incidence of primary spontaneous pneumothorax is estimated to be approximately 7.4-18 per 100 000 per year for men and approximately 1.2-6 per 100 000 per year for women.[1,2] It has been noted that the typical person who presents with a spontaneous pneumothorax has an asthenic body habitus, being taller and thinner than the average person.[3]

Radiographic and thoracoscopic examinations of patients with primary spontaneous pneumothoraces often reveal underlying subtle lung abnormalities in the form of blebs, bullae, and cysts. Blebs and bullae were discovered on the affected side 76% of the time when a video-assisted thoracoscopic surgery (VATS) procedure was performed, and 100% of the time when thoracotomy or sternotomy was performed.[4] Given this association, primary spontaneous pneumothorax has been considered a form of distal acinar emphysema. In this subtype of emphysema, the airspace enlargement is confined to subpleural or paraseptal locations, so that most of the lung parenchyma is spared. The disease is clinically silent, unless one of the blebs ruptures and causes a pneumothorax. The pathogenesis of the blebs is not well understood but has been attributed to congenital abnormalities,[5] increased mechanical stresses at the apex in the upright lung,[6] and bronchiolar inflammation and fibrosis.[7] As is the case for the more common form of emphysema, the expression of primary spontaneous pneumothorax is related to the amount and duration of smoking. The relative risk of pneumothorax is 7 times higher in light smokers (defined as smoking 1-12 cigarettes per day), 21 times higher in moderate smokers (13-22 cigarettes per day), and over 80 times higher in heavy smokers (> 22 cigarettes per day).[8]


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