Birt-Hogg-Dubé Syndrome: The experience of an Italian Centre

Abstract

Birt-Hogg-Dube Syndrome (BHDS) is an autosomal dominant inherited disorder characterized by pulmonary cysts with recurrent spontaneous pneumothorax (PNX), increased risk of developing malignant renal neoplasms and skin lesions. BHDS-associated gene locus was localised in chromosome 17p11.2 and the novel gene Folliculin was subsequently identified as being inactivated in individuals with BHDS. The prevalence of disease is likely underestimated due to the paucity of data available nowadays. From July 2014 till December 2016 we consecutively studied all patients with familial spontaneous PNX referring to our Institution. Family history of PNX represented the main criteria to raise the clinical suspicion. 6 index cases were identified and the corresponding 6 families with 13 family members were studied. 13/19 cases had a positive genetic analysis and on chest CT scan all 6 index cases as well as 7 family members had pulmonary cysts. Most patients (6/13, 46.15%) had innumerable bilateral cysts with a clear lower lobe predominance and diameter greater than 2cm. All cysts were rounded-oval in shape, had thin margins and were paramediastinal and perifissural in almost all cases (12/13, 92.31% and 11/13, 84.61%). Skin lesions, including fibrofolliculomas and trichodiscomas, were present in 7/13(53.85%) patients, while renal cysts in 4/13 (30.77%). A single patient (1/13, 7.69%) developed renal cancer at the age of 46. Our study demonstrates that this rare disease is probably under-diagnosed in Italy as well as in Europe and it should be sought in all patients with familial PNX associated with dermatological and renal lesions. A prompt diagnosis of BHDS is necessary to improve the prognosis of these patients and their families.