Birt–Hogg–Dubé (BHD) is a rare autosomal dominant inherited syndrome that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. Here, the 2 patients we reported with renal cell carcinomas and dermatological features were suspected to be suffering from BHD syndrome. Blood samples of these patients were sent for whole exon sequencing performed by Sanger sequencing. Eight mutations, including 5 mutations, which were mapped in noncoding region, 1 synonymous mutation, and 2 missense mutations, were detected in the FLCN gene in both patients. The 2 missense mutations, predicted to be disease-causing mutation or affecting protein function by MutationTaster and SIFT, confirmed the diagnosis. In addition, the 2 patients were also affected with papillary thyroid cancer. Total thyroidectomy and prophylactic bilateral central lymph node dissection were performed for them and the BHD-2 also received lateral lymph node dissection. Pathology reports showed that the patients had lymph node metastasis in spite of small size of thyroid lesions.
The 2 missense mutations, not reported previously, expand the mutation spectrum of FLCN gene associated with BHD syndrome. For the thyroid cancer patients with BHD syndrome, total thyroidectomy and prophylactic bilateral central lymph node dissection may be suitable and the neck ultrasound may benefit BHD patients and their family members.