Birt Hogg-Dubé syndrome in Poland

Abstract

Birt Hogg-Dube syndrome (BHDS) is a rare, autosomal, dominant inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterized by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothorax, and renal tumors. The aim of the study was to present the features of Polish patients with BHDS. Material and Methods: The first case of BHDS was published in Poland in 2016. Since that time 10 other cases form 6 families were identified. Diagnosis was confirmed by direct sequencing of the folliculin gene in ten patients, and in one according to characteristic clinical, radiological presentation and skin biopsy. Results: BHDS was diagnosed in 9 women and 2 men.The mean age in the time of first symptoms, and diagnosis were 34.8 ±13.2 and 41.3 ±14.2 years respectively. Only one woman was ex-smoker (1,5 packyears), but ten patients never smoked cigarettes. Eight patients (66.7%) had a history of recurrent pneumothorax. One patient had small, asymptomatic pneumothoraxes, which were detected only on CT examination. Skin lesions were detected in 4 (36.0%) patients, and no renal lesions have been shown. All patients had multiple, bilateral pulmonary cysts, distributed in predominantly lower, peripheral and subpleural regions of lungs. In all families different mutations of the FLCN gene were identified, with two novel heterozygous sequence variants of c.490delA(p.Arg164GlyTer13), and c.40delC(p.His14ThrsfTer41). Patients showed preserved lung function that remained unchanged during the follow-up. Conclusion: Polish patients with BHD syndrome presented different clinical features with less frequent renal lesions, and with high percentage of novel FLCN mutations then patients form other populations