FOLLICULIN GENE MUTATION IN A YOUNG WOMAN WITH RECURRENT PNEUMOTHORAX

Abstract

Listen

Translate article

TOPIC: Genetic and Developmental Disorders TYPE: Medical Student/Resident Case Reports INTRODUCTION: Folliculin (FLCN) gene mutation, commonly linked with Birt-Hogg-Dube (BHD) syndrome, is associated with primary spontaneous pneumothorax (PSP). PSP is defined by air in the pleural space in those without a history of lung disease or trauma. A pneumothorax (PTX) can be a life-threatening condition that requires immediate tube thoracostomy placement. Here, we present a case of recurrent PSP in a woman presenting with dyspnea. CASE PRESENTATION: A 36-year-old woman non-smoker with a history of unclassified bullous lung disease and recurrent PTX status post right video assisted thoracoscopic surgery (VATS) with mechanical pleurodesis and left VATS with talc pleurodesis presented to the emergency department (ED) with progressive dyspnea. Family history was notable for bullous lung disease and PTX in her maternal grandfather and mother. Days prior to ED, she developed right sided pleuritic chest pain after yoga that self-resolved. Chest radiography revealed right sided pleural effusion without signs of PTX. A day prior to the ED, she developed dyspnea with exertion. On admission, she was at 100% saturation on room air, normotensive and had decreased breath sounds in her right lower lung field. Computed tomography (CT) revealed a new large right basilar, anterior, medial PTX and redemonstration of multiple bilateral bullae unchanged from prior imaging. VATS was recommended but refused. A 10.3 French chest tube was placed to wall suction overnight. Repeat CT revealed near complete resolution of the PTX with unchanged bullae. Genetics workup revealed an FLCN mutation c.1584del; p.Glu530Argfs*7 suggesting the cause of recurrent PTX. DISCUSSION: A diagnosis of PSP requires the exclusion of lung diseases such as cystic fibrosis and alpha-1-antitrypsin, connective tissue disorders such sjogren's and marfan syndromes, rare conditions such as lymphangioleiomyomatosis and tuberous sclerosis. PSP commonly occurs due to rupture of subpleural bullae and can be a complication of BHD syndrome. BHD syndrome is a hereditary cancer disorder characterized by renal cell cancer, colonic polyps, hair follicle hamartomas, lung cysts and PTX. It is associated with a FLCN gene mutation, which is expressed in type I pneumocytes that form the structure of alveoli. FLCN mutation lung cysts are hypothesized to be due to a defect in cell-cell adhesion resulting in expansion of alveolar spaces. FLCN mutation patients can rarely present with a purely spontaneous PTX. PSP treatment options include a chest tube (recurrence rate (RR) 26.4%), VATS pleurectomy (RR 0.4%), VATS abrasion (RR 2.3%) and lung transplantation. CONCLUSIONS: A FLCN gene mutation should be excluded in those with recurrent PTX. Genetic testing should be considered as well as appropriate cancer screening with renal ultrasound and colonoscopy given its association with BHD. REFERENCE #1: Boone, P. M. et al. (2019). The genetics of pneumothorax. AJRCCM, 199(11), 1344-1357. REFERENCE #2: Daccord, C. et al. (2020). Birt–Hogg–Dubé syndrome. European Respiratory Review, 29(157), 200042. REFERENCE #3: Frohlich, B. et al. (2008). Novel mutations in the folliculin gene associated with spontaneous pneumothorax. European Respiratory Journal, 32(5), 1316-1320. DISCLOSURES: No relevant relationships by George Moran, source=Web Response No relevant relationships by Hekmat Nasiri, source=Web Response No relevant relationships by Sudhir Rajan, source=Web Response