Etiology of Primary Spontaneous pneumothorax in Children and Adolescents

Objectives-aim: Primary Spontaneous pneumothorax (PSP) is a spontaneous pneumothorax that occurs in patients with no known underlying lung disease. We aimed to describe clinical phenotypes and investigate possible underlying genetic causes to demonstrate the etiology of childhood PSP. <bold>Methods:</bold> A prospective cohort study was conducted on PSP patients under 18 years old. Clinical characteristics of patients were recorded. Exome sequencing was performed, and results were evaluated in terms of pathogenic variants. <bold>Results:</bold> Twenty patients (19 male, 1 female) were included in the study. The median age at the time of the first PSP was 15.5 years (range:1.5-17.0). Recurrence was seen in 12 patients. A positive family history of pneumothorax was elicited in 2 patients. Likely pathogenic, missense variants in 5 genes (COL1A2, COL11A2, COL3A1, MHY 11, ACTA2) were identified in 6 patients from 6 unrelated families. These patients experienced recurrent PSP, and 2 of the 6 had a positive family history. Segregation analyses within the families revealed that one patient had a de-novo variant (COL3A1), and one patient had a paternally inherited ACTA2 variant in which the father had a history of aortic rupture. <bold>Conclusion:</bold> The study reveals pathogenic, missense variants in several connective tissue-related genes in patients with PSP. Recurrence and positive family history suggest a genetic etiology in patients with PSP. Pathogenic variants in COL3A1 and ACTA2 may be responsible for PSP etiology.