Delayed Birt-Hogg-Dube syndrome diagnosis in the absence of telltale skin lesions

Introduction: Birt-Hogg-Dube syndrome is an extremely rare genetic disorder associated with skin lesions, lung cysts, pneumothorax and a high incidence of renal cell carcinoma. Clinical diagnosis is usually suspected by recognition of the typical papular skin lesions (fibrofolliculomas, present in about 80% of patients). We present a case of delayed BHD syndrome diagnosis in a patient lacking the telltale skin lesions. Case Report: A 47-year old female, never smoker, presented with a spontaneous left-sided pneumothorax. Medical history revealed a leftsided pneumothorax at age 26. At age 27 she underwent a leftsided nefrectomy for renal cell carcinoma. At age 38 she had a rightsided pneumothorax. The patient had no skin lesions. HRCT showed multiple bilateral, predominantly basally located lung cysts. VATS with bullectomy and pleurectomy was performed succesfully, to treat the recurrent left-sided pneumothorax. The postoperative course was uneventful. Microscopic investigation of the resected lung tissue showed normal lungparenchym and the presence of a bulla. The occurence of multiple lung cysts along with a recurrent pneumothorax and history of renal cancer in a non-smoking female raised the possibility of BHD-syndrome. Subsequent genetic testing confirmed the diagnosis by demonstrating an insertion-deletion (indel-) mutation in the FLCN gene (c.610_611delinsTA). Since the BHD syndrome diagnosis, the patient now undergoes annual screening for renal cancer using MRI. Discussion: The absence of telltale skin lesions can delay a BHD syndrome diagnosis. Timely recognition of the BHD syndrome enables periodic screening and early detection of renal cancer in patients and affected relatives.