Feng Jingjing, Yu Yunxia, Liu Yi, Ding Yi, Mu Junyi, Jiang Rong, Sharma Lokesh, Jie Zhijun
Center of Community-Based Health Research, Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Shanghai Public Health Clinical Center, Shanghai Emerging and Re-Emerging Institute, Fudan University, Shanghai, China.
Front Med (Lausanne). 2025 Jun 24;12:1581786. doi: 10.3389/fmed.2025.1581786. eCollection 2025.
The Birt-Hogg-Dubé (BHD) syndrome is a rare, autosomal dominant disorder caused by germline mutations in the FLCN gene, which encodes a tumor suppressor protein. The syndrome is characterized by cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothoraces, and renal tumors. We report a rare familial case of BHD complicated by primary lung adenocarcinoma in a 69-year-old man. The patient presented with a persistent cough, bilateral pulmonary cysts, and a 4 × 3 cm tumor in the left lung lobe. Genetic testing revealed a novel pathogenic FLCN mutation (c.295_311del p.Asp99Ter) in the patient and several family members, including his son and brother, both of whom exhibited pulmonary cysts and histories of pneumothoraces. The patient was diagnosed with invasive lung adenocarcinoma. Although tumor progression was stabilized with treatment, the clinical course was complicated by severe hyperthyroidism, liver injury, and myelosuppression. This case highlights the complexities of managing lung cancer in BHD patients and suggests a potential role for FLCN mutations in tumorigenesis. Our findings underscore the importance of early diagnosis, genetic testing, and a multidisciplinary approach to the management of BHD in order to improve patient outcomes and prevent complications. In addition, we conducted a literature review of previously reported FLCN mutations in BHD syndrome.
Birt-Hogg-Dubé（BHD）综合征是一种罕见的常染色体显性疾病，由FLCN基因突变引起，该基因编码一种肿瘤抑制蛋白。该综合征的特征为皮肤纤维毛囊瘤、肺囊肿、自发性气胸和肾肿瘤。我们报告了一例69岁男性的罕见家族性BHD病例，该病例并发原发性肺腺癌。患者表现为持续性咳嗽、双侧肺囊肿以及左肺叶一个4×3厘米的肿瘤。基因检测发现患者及其包括儿子和兄弟在内的几名家庭成员存在一种新的致病性FLCN突变（c.295_311del p.Asp99Ter），其儿子和兄弟均有肺囊肿和气胸病史。患者被诊断为浸润性肺腺癌。尽管治疗后肿瘤进展得到稳定，但临床过程因严重甲状腺功能亢进、肝损伤和骨髓抑制而变得复杂。该病例凸显了BHD患者肺癌管理的复杂性，并提示FLCN突变在肿瘤发生中可能发挥的作用。我们的研究结果强调了早期诊断、基因检测以及多学科方法管理BHD以改善患者预后和预防并发症的重要性。此外，我们对先前报道的BHD综合征中FLCN突变进行了文献综述。
