Pulmonary features of Birt-Hogg-Dubé syndrome: Cystic lesions and pulmonary histiocytoma

Summary Background to describe clinical, radiologic and pathologic features of lung lesions in Birt-Hogg-Dube syndrome (BHDS) (MIM 135150). Method review of 12 patients of BHDS from 3 unrelated Italian families evaluated at GB Morgagni Hospital, Forli, from 2005 to 2010. Results mean age (±SD) at diagnosis was 44.6 (±16) years, 8 (66%) were male. All three index cases presented with a history of recurrent pneumothorax and/or cystic lung lesions evaluated by CT scan request by referring pulmonary physicians, none were diagnosed to have BHDS at the time of initial pulmonary evaluation. One of the three cases was a middle-aged female patient with a clinical phenotype indistinguishable from lymphangioleiomyomatosis (LAM), characterized by cystic lung lesions and kidney angiomyolipoma. In one case of BHDS presenting with recurrent pneumothorax and a solitary lung nodule, surgical lung resection revealed a pulmonary histiocytoma. In one case a novel mutation of BHD gene was detected (c.771 del, exon 7). Conclusions BHDS is associated with cystic lung disease largely under-recognized by pulmonary physicians and can mimic LAM and may be associated with lung tumor, pulmonary histiocytoma. In one case we found a novel mutation in exon 7, c.771 del (ref.seq. NM_144997.5) never reported before.