A RARE AND LATE PRESENTATION OF A HEREDITARY CYSTIC LUNG DISEASE

Abstract

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant condition, initially identified in 1977. It is characterized by benign skin hamartomas, pulmonary cysts, spontaneous pneumothoraces, and increased risk of renal cancer. We hereby present a rare case of BHD that was incidentally diagnosed in a 74-year-old female. CASE PRESENTATION: A 74-year-old female with past medical history of mild intermittent asthma, Crohn’s disease, 15 pack-year smoking history, and basal cell carcinoma presented for follow-up in pulmonology clinic after hospitalization for a primary spontaneous pneumothorax. She reported occasional mild shortness of breath and chest tightness which was previously attributed to seasonal allergies and asthma. She subsequently underwent high resolution CT imaging showing cystic lung disease with predominantly bibasilar distribution of thin-walled cysts. On further review, bilateral renal cysts were identified. At this point she was suspected of having pulmonary lymphangioleiomyatosis (LAM). Family history revealed that the patient’s father and sister also had a history of pneumothorax. On physical exam the patient was noted to have flesh colored nodules on her forehead and neck regions suggestive of fibrofolliculoma or trichodiscoma. Autoimmune testing was negative and VEGF-D testing was negative. The patient was screened for genetic markers for cystic lung disease with a pathogenic mutation identified in the folliculin (FLCN) gene. Family history, imaging, and physical exam all led to a diagnosis of BHD syndrome, with final confirmation obtained from genetic testing. DISCUSSION: BHD syndrome results from a genetic germline mutation in the FLCN gene, which encodes the protein folliculin, and is considered to be a tumor suppressor gene. Incidence of BHD syndrome is unknown, with approximately 500 families identified worldwide. FLCN mutation penetrance in affected families is high, however the presence of physical manifestations varies drastically. The penetrance of renal cancer is relatively low, but confers a seven-fold increased risk compared to the general population. CONCLUSIONS: BHD is a genetic multi-system disorder associated with cystic lung changes, cutaneous manifestations, recurrent pneumothoraces, and renal cysts and neoplasms. Genetic testing is indicated for family members when an FLCN mutation is identified in a first-degree relative. Lifelong surveillance for renal cancers is essential. Imaging modalities recommended include CT or MRI imaging of the abdomen. Reference #1: Schmidt LS, Linehan WM. Molecular genetics and clinical features of Birt-Hogg-Dube syndrome. Nat Rev Urol 2015; 12:558. Reference #2: Gupta N, Seyama K, McCormack FX. Pulmonary manifestations of Birt-Hogg-Dubé syndrome. Fam Cancer 2013; 12:387. Reference #3: Stamatakis L, Metwalli AR, Middelton LA, Marston Linehan W. Diagnosis and management of BHD-associated kidney cancer. Fam Cancer 2013; 12:397. DISCLOSURES: No relevant relationships by Aadil Ahmed, source=Web Response No relevant relationships by Roselle Almeida, source=Web Response No relevant relationships by daniel kechker, source=Web Response No relevant relationships by Samrat Khanna, source=Web Response