Prior imaging after spontaneous pneumothoraces revealed cystic lung disease, which was treated with bilateral bullectomies and pleurodesis. Lower lobe predominant cysts are more often caused by desquamative interstitial pneumonia (DIP), a smoking-related process, or lymphocytic interstitial pneumonitis (LIP), a lymphoproliferative process with known risk factors. The absence of risk factors for DIP and LIP and the absence of other pulmonary parenchymal abnormalities argues against these diagnoses. Considering the history of multiple family members with similar spontaneous pneumothoraces and cystic lung disease, a heritable disease would be a possible diagnosis. While rare, Birt-Hogg-Dubé syndrome is an autosomal dominant syndrome that causes lower lobe predominant cysts, chromophobe renal cell carcinoma, renal oncocytomas, and cutaneous hair follicle hamartomas.
Genetic testing in this patient revealed the patient was heterozygous for a single duplication within the gene for a protein called Folliculin (FLCN) that resulted in a frameshift mutation and a premature stop codon. This mutation is reported in almost half of patients with Birt-Hogg-Dubé syndrome.