Two families with Birt-Hogg-Dubé syndrome:case report and literature review

Abstract

Objective: To improve the awareness of Birt-Hogg-Dubé syndrome. Methods: We performed a retrospective analysis with two families of Birt-Hogg-Dubé syndrome (BHD syndrome) diagnosed in Department of Respiratory and Critical Care Medicine, Shenzhen People's Hospital from 2020 to 2021. Clinical manifestations, imaging features, diagnosis and gene detection results were summarized. Relative literatures were reviewed in Wanfang Database and PubMed from 2015 to 2021 by using the search terms of "BHD syndrome" "Birt-Hogg-Dubé" "Birt-Hogg-Dubé syndrome", respectively. Results: The probands of both families were female, aged 37 and 34 years respectively. The onset manifestation was pulmonary bullae combined with pneumothorax. Chest computed tomography (CT) imaging showed multiple pulmonary cysts in both lobes, and no skin lesions or renal tumors were found in either case. History of pneumothorax was present in Family 1 while absent in Family 2. The FLCN gene of the two probands and their relatives showed the same mutation site. Totally 12 Chinese literatures and 394 English literatures were retrieved, among which 96 reported lung involvement only. A total of 10 literatures about Chinese population were screened out from the English literatures, and 115 patients, 31 males and 84 females, were included. The incidence of spontaneous pneumothorax was 66.95% (77/115), while a family history of pneumothorax was 88.31%(68/77). The onset age of spontaneous pneumothorax was between 30 and 44 years. The most common mutation site of FLCN was c.1285dup. Conclusions: BHD syndrome in Asian population may only have lung involvement. Patients with pneumothorax and pulmonary cystic lesions should be inquired of the family history. We speculate that there are many underdiagnosed cases in clinical practice.