Birt-Hogg-Dube syndrome - A novel marker of kidney neoplasia

Background: Birt-Hogg-Dube syndrome (BHD) is a dominantly inherited predisp osition for development of fibrofolliculomas, trichodiscomas, and acrochord ons. Concurrent internal tumors, such as colonic polyps and renal carcinoma , have been described in patients with BHD. Objective: To evaluate kindreds with familial renal tumors for cutaneous ma nifestations of BHD. Design: One hundred fifty-two patients from 49 families underwent complete oral and skin examination. Skin lesions were identified by their clinical a ppearance. and the diagnosis was confirmed by results of histologic examina tion. Individuals underwent screening for familial renal neoplasms. Setting: A tertiary referral research hospital. Patients: Individuals with familial renal tumors and their asymptomatic at- risk relatives. Main Outcome Measure: Wt determined whether any form of renal cancer is ass ociated BHD. Results: We identified 3 extended kindreds in whom renal neoplasms and BHD appeared to segregate together. Two kindreds had renal oncocytomas and a th ird had a variant of papillary renal cell carcinoma. Thirteen patients exhi bited BHD. Seven individuals, including a set of identical twins, had renal neoplasms and BHD. An additional 4 patients (3 deceased and nor examined) in these families had renal neoplasms but not BHD. Birt-Hogg-Dube syndrome without renal neoplasms was present in 6 individuals. Thirteen patients wit h fibrofolliculomas and trichodiscomas presented clinically with multiple s mooth skin-colored to grayish-white papules located on the face, auricles, neck, and upper trunk. Oral papules were present in 9 of 28 and achrochordo ns in 11 of 28 patients. Features of BHD not previously appreciated include d deforming lipomas in 5, collagenomas in 4, and pulmonary cysts in 4 of 28 patients. Families with BHD did not display germline mutations in the von Hippel-Lindau gene or in the tyrosine kinase domain of the MET proto-oncoge ne. Conclusions: Birt-Hogg-Dube syndrome may be associated with familial renal tumors. Birt-Hogg-Dube and renal tumors segregate together in an autosomal dominant fashion, Patients with BHD and their relatives are at risk for dev elopment of renal tumors. Therefore, patients with BHD and their relatives should undergo abdominal computed tomography and renal ultrasound screening for renal tumors.