Birt-Hogg-Dubé Syndrome - report of two cases with two new mutations.

INTRODUCTION: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by cutaneous fibrofolliculomas and/or trichodiscomas, lung cysts, spontaneous pneumothorax and renal tumors. However, its clinical expression is highly variable. This syndrome is caused by germline mutations in the folliculin gene ( FLCN ) on chromosome 17p11.2.

MAIN OBSERVATIONS: Two men, 60 and 39-year-old, presented with a several year history of asymptomatic whitish papules scattered over the face and neck. Skin biopsies revealed fibrofolliculomas. The clinical diagnosis of BHDS was corroborated by identification of new heterozygotic mutations in FLCN gene, in exon 6 (C.573_574delinsT) and in exon 9 (c.1015C>T), respectively. Computed tomography scan of the thorax and abdomen showed pulmonary cysts with no suspicious kidneys lesions, and, in the case of the second patient, a mass in left adrenal gland. Laparoscopic left adrenalectomy was performed and histopathological examination was compatible with a malignant perivascular epithelioid cell tumor.

CONCLUSIONS: The presence of multiple fibrofolliculomas should raise the suspicion of BHDS. Patients with this syndrome, regardless of the detected mutation, should be carefully monitored to ensure that potentially serious disease-related conditions can be detected early.