From the Research
Spontaneous pneumothorax has several genetic causes, with the most significant being mutations in genes related to connective tissue disorders, as highlighted in a recent review 1. The genetic causes of spontaneous pneumothorax can be attributed to various syndromes, including:
- Birt-Hogg-Dubé syndrome, caused by mutations in the FLCN gene, which is strongly associated with recurrent spontaneous pneumothorax
- Marfan syndrome (FBN1 gene mutations)
- Ehlers-Danlos syndrome (various collagen gene mutations)
- Alpha-1 antitrypsin deficiency (SERPINA1 gene)
- Lymphangioleiomyomatosis, linked to TSC1 and TSC2 mutations, which predominantly affects women and causes multiple lung cysts that can rupture These genetic conditions typically cause structural abnormalities in lung tissue, creating thin-walled air sacs or cysts that rupture easily, allowing air to escape into the pleural space. A study published in 2020 found a high prevalence of alpha-1 antitrypsin deficiency in patients with spontaneous pneumothorax, with 26% of patients presenting with AAT serum concentrations ≤ 120 mg/dl and 12% having deficiency variants 2. Patients with a family history of pneumothorax or these genetic disorders should be monitored closely, and genetic counseling may be appropriate, as early identification of these genetic causes can help with preventive management and treatment planning for affected individuals 1. Key points to consider in the management of spontaneous pneumothorax include:
- Computed tomography screening for underlying disease should be considered in patients who present with spontaneous pneumothorax 3
- Conservative management may be appropriate for selected stable patients, with similar recurrence rates and less complications compared to invasive interventions 3
- Genetic testing and evaluation by a geneticist may be warranted in cases where a genetic or familial contribution is suspected 1