A splicing mutation of the FLCN gene is associated with Birt-Hogg-Dubé syndrome characterized by familial and recurrent spontaneous pneumothorax: A case report.

Rationale: Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal recessive genetic disorder caused mainly by mutations in the tumor suppressor FLCN gene. Tumors caused by FLCN mutations are frequently benign and develop in skin, lungs, kidney, and other organs, leading to a variety of phenotypes that make early diagnoses of BHD challenging.

Patient Concerns: A 51-year-old female was admitted to Shanghai Seventh People Hospital due to chest congestion and dyspnea that had persisted for 3 years and aggravated for 1 month. She had been diagnosed with pneumothorax prior to this submission, but the etiology was unknown.

Diagnoses: Chest computed tomography (CT) revealed multiple pulmonary cysts and pneumothorax, and her family members shared similar manifestation. Whole-exome sequencing analysis indicated a heterozygous FLCN splicing mutation (c.1432 + 1G > A; rs755959303), which was a pathogenic variant indicated in ClinVar. Based on FLCN mutation and the family history of pulmonary cysts and pneumothorax, BHD syndrome was finally diagnosed, which had been delayed for 3 years since her first pneumothorax.

Interventions: Pulmonary bullectomy and pleurodesis were finally conducted due to the poor effects of thoracic close drainage.

Outcomes: Her pneumothorax was resolved, and no recurrence was found in 2 years.

Lessons: Our study highlights the importance of genetic analysis in diagnosis and clinical management of BHD syndrome.