Inherited predisposition to pneumothorax: estimating the frequency of Birt-Hogg-Dubé syndrome from genomics and population cohorts

• DOI: 10.1136/thorax-2024-221738
• Publication Date: 2025-04-10T15:35:16Z
• Authors: Bryndis Yngvadottir; Lucy Richman; Avgi Andreou; Jessica Woodley; Anita Luharia; Derek Lim; ; Eamonn R Maher; Stefan J Marciniak
• Keywords: Folliculin; Birt–Hogg–Dubé syndrome

Birt-Hogg-Dubé syndrome (BHDS) is the most common monogenic cause of pneumothorax. Most affected families have pathogenic variants in FLCN gene. Using large genomic registries (UK Biobank (UKB), 100,000 Genomes Project and East London Genes & Health) including >550 000 individuals, we demonstrate that frequency clinically validated loss-of-function 1 2710 to 4190. While lifetime risk pneumothorax mutation carriers UKB a BHDS clinical cohort was substantial (28.4% 37.3%, respectively, age 65 years), renal cancer significantly lower than patients (1% vs 32.1%). These findings highlight importance context managing individuals with mutations.