Birt-Hogg-Dubé syndrome presenting with spontaneous pneumothorax and extensive pulmonary cysts in the absence of skin lesions or renal pathology

Abstract

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition which classically manifests with skin lesions such as fibrofolliculomas, pulmonary cysts that predispose to spontaneous pneumothorax and an increased risk of developing renal cell carcinoma. We describe the case of a patient who presented with a spontaneous pneumothorax on a background of multiple lung cysts, in the absence of cutaneous fibrofolliculomas and renal tumours. A germline mutation in the folliculin FLCN gene was subsequently identified, confirming BHD syndrome. Our case highlights the importance of considering a broad differential diagnosis for the cause of a spontaneous pneumothorax in the presence of unexplained cystic lung disease and emphasises the value of maintaining a high index of clinical suspicion for inherited causes of pneumothoraces.

A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours

“…Overall, 50.9% (528/1038) of reported individuals had experienced at least one pneumothorax (Table 1 ) [ 2 , 4 – 6 , 8 – 41 ]. Of these, 66.7% (220/330) had recurrent pneumothoraces.…”

“…Of the patients who underwent thoracic CT imaging, 92.1% (662/720) had reported lung cysts. Of these patients, 63.7% had a pneumothorax [ 2 , 4 – 6 , 8 – 18 , 21 – 28 , 30 , 31 , 34 – 41 ].…”

“…Of the 989 patients with recorded dermatological examinations, 47.9% had lesions consistent with BHDS [ 2 , 4 – 6 , 8 – 18 , 20 – 41 ]. Most had fibrofolliculomas (90.5%; 429/474), 8.8% (42/474) had trichodiscomas and 4.0% (19/474) had perifollicular adenomas.…”

“…Since renal malignancy can often be cured by early surgery, annual surveillance for small malignant renal tumours has been recommended in individuals with BHDS [ 3 ]. In addition to individuals diagnosed with BHDS, pathogenic FLCN variants have also been described in individuals with familial pneumothorax but no other features of BHDS [ 4 – 6 ]. In some cases, it has been suggested that specific FLCN variants could result in a pneumothorax-only phenotype [ 4 – 6 ].…”

“…In addition to individuals diagnosed with BHDS, pathogenic FLCN variants have also been described in individuals with familial pneumothorax but no other features of BHDS [ 4 – 6 ]. In some cases, it has been suggested that specific FLCN variants could result in a pneumothorax-only phenotype [ 4 – 6 ]. Most FLCN variants are truncating and will therefore cause loss of function.…”