Why Patients with Marfan Syndrome Have Increased Risk for Spontaneous Pneumothorax
Patients with Marfan syndrome develop spontaneous pneumothorax due to structural lung abnormalities—specifically apical blebs and bullae—that result from the underlying connective tissue defect caused by fibrillin-1 deficiency. 1
Pathophysiologic Mechanism
The fundamental problem lies in the genetic mutation affecting connective tissue integrity:
Marfan syndrome results from mutations in the FBN1 gene encoding fibrillin-1, a glycoprotein in the extracellular matrix that provides structural support to tissues throughout the body. 1
Fibrillin-1 deficiency leads to weakening of supportive tissues, including those in the lung parenchyma, making the pleural surface vulnerable to rupture. 1
This connective tissue weakness manifests in the lungs as apical blebs and bullae—thin-walled air-filled spaces that are prone to spontaneous rupture. 2, 3
Clinical Epidemiology and Risk Stratification
The actual risk of pneumothorax in Marfan patients is well-defined:
Spontaneous pneumothorax occurs in 4-11% of patients with Marfan syndrome, with most studies converging around 4.4-4.8%. 4, 2, 3
The presence of radiologically detectable apical blebs or bullae dramatically increases risk: 25% of patients with visible blebs develop pneumothorax compared to only 2.7% without blebs (p=0.003). 3
Men are more commonly affected than women, though disease severity is similar between sexes. 2
Recurrence is extremely common—approximately 64% of patients (7 of 11 in one series) experience recurrent or bilateral pneumothorax if not definitively treated. 2
Radiologic Detection of High-Risk Features
Apical blebs and bullae are detectable on chest radiography in approximately 82% of patients who develop pneumothorax (9 of 11 patients in one series). 2
However, the sensitivity of plain radiography is limited:
Only 9.6% of all Marfan patients have radiologically detectable blebs or bullae on imaging studies, suggesting many smaller lesions go undetected on chest X-ray. 3
CT scanning provides superior detection of blebs and bullae, allowing better risk stratification for pneumothorax in Marfan patients. 3
Clinical Recognition and Diagnostic Pitfalls
Spontaneous pneumothorax may be the presenting manifestation of previously undiagnosed Marfan syndrome, particularly in adolescents and young adults. 4, 5
Critical diagnostic considerations include:
The British Thoracic Society recommends that approximately 10% of pneumothorax cases have a family history, and clinicians should actively seek familial causes including Marfan syndrome, Birt-Hogg-Dubé syndrome, and Ehlers-Danlos syndrome. 1
When familial pneumothorax is suspected, CT imaging should always be part of the standard workup, and referral to specialists or pneumothorax clinics should be considered. 1
Physical examination should specifically assess for marfanoid habitus, including skeletal abnormalities such as pectus excavatum, straight thoracic spine, and characteristic body proportions. 1, 4
Management Implications
Definitive surgical treatment should be performed at the first occurrence of pneumothorax in Marfan patients because of the high recurrence rate (>60%) after conservative management with chest tube alone. 2
The recommended surgical approach includes:
Resection of the offending bullae combined with pleurodesis to prevent recurrence. 2, 5
Video-assisted thoracoscopic surgery (VATS) for bullectomy and pleurodesis is the preferred minimally invasive approach. 5
Simple chest tube drainage without definitive surgery results in unacceptably high recurrence rates. 2
Screening Recommendations
All adolescent and adult patients with Marfan syndrome should undergo chest radiography to assess for apical blebs and bullae, allowing identification of high-risk patients. 2