Birt-Hogg Dubé Syndrome: Prevalence and Clinical Characteristics Determined from a National Referral Centre

<bold>Introduction:</bold> Birt-Hogg Dube Syndrome (BHD) is a rare autosomal dominant condition caused by pathogenic variants in the folliculin (FLCN) gene. There is a wide heterogeneity in phenotype. Reported worldwide prevalence is 2 cases per million. The aims of this study were to estimate BHD prevalence in a single country, and examine correlation between lung function, CT scans and clinical outcomes. <bold>Methods:</bold> Data for BHD patients was identified and collated from the ERN-Lung centre at St. Vincent’s University Hospital, Dublin. <bold>Results:</bold>51 cases of BHD were identified; 43%(n=22) male and 57%(n=29) female. Median age was 51 years (range 17-82). Referrals were made for pneumothorax (29%,n=15), incidental pulmonary cysts on imaging(27%,n=14),screening due to family history (37%,n=19), fibrofolliculomas(4%,n=2) and due to kidney lesions (2%, n=1). The most common genotypes were c.17_21del (18%),c.1285dupC (10%) and c.469_471del (4%).25%(n=13) have fibrofolliculoma and 16%(n=8) have renal lesions.41%(n=21) had history of pneumothorax. There was no correlation between pneumothorax and gene variant. Mean FEV1 and DLCO were 90.80% (SD+/-13.02) and 78.41% (SD+/-15.64)respectively. Mean cyst burden score was 2% of total lung volume (range 0.1-5.4%). Cyst burden did not correlate with FEV1%(R2=0.079,p=0.429) or DLCO(R2=0.023,p=0.676). Patients with history of pneumothorax were more likely to have higher cyst burden score independent of lung function (mean=2.37% vs 0.9%,p=0.08). <bold>Conclusion:</bold> BHD is likely under-recognised. While reported prevalence worldwide is 2 cases per million, we identified 51 individuals with BHD in our clinic, representing a minimum estimate of 10.13 cases per million