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Birt-Hogg-Dubé syndrome

Author
Edward W Cowen, MD, MHSc
Section Editor
Jonathan A Dyer, MD
Deputy Editor
Rosamaria Corona, MD, DSc

INTRODUCTION

Birt-Hogg-Dubé syndrome (BHD, MIM #135150) is an autosomal dominant condition first described in 1977, characterized by benign skin hamartomas, most commonly located on the head and neck; pulmonary cysts and spontaneous pneumothorax; and an increased risk of renal cancer. BHD syndrome is caused by germline mutations in the folliculin gene (FLCN), which encodes the protein folliculin, a putative tumor suppressor gene whose function is still under investigation.

This topic review will discuss the pathogenesis, clinical features, diagnosis, and management of BHD syndrome. Renal tumors and other inherited renal cancer syndromes are discussed separately. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma" and "Hereditary kidney cancer syndromes".)

EPIDEMIOLOGY

The incidence of BHD syndrome is unknown. Approximately 200 families have been identified worldwide [1]. The overall penetrance of folliculin (FLCN) mutations in affected families is high; however, the presence of cutaneous, pulmonary, and renal manifestations varies significantly, even within families. Although the penetrance of renal cancer is relatively low, patients with BHD syndrome have a sevenfold increased risk of kidney tumors compared with the general population [2].

In a review of 89 patients with BHD syndrome from 51 families from the National Institutes of Health (NIH), cutaneous lesions were found in 90 percent of patients, pulmonary cysts in 84 percent, and history of pneumothorax in 38 percent [3]. Renal tumors were found in 30 patients from 25 families, indicating that most families with renal tumors had only one member affected, even after screening for renal tumors all carriers of FLCN mutations with abdominal computed tomography (CT) or magnetic resonance imaging (MRI) of the kidneys.

PATHOGENESIS

BHD syndrome is caused by germline mutations in the folliculin (FLCN) gene, located on chromosome 17p11.2. These mutations are small insertion/deletions, splice-site, and nonsense mutations, which lead in most cases to premature truncation and loss of function of the folliculin protein [4]. To date, 149 unique FLCN germline mutations spanning all 14 exons have been identified in BHD families and catalogued in the Leiden Open Variation Database.

                            

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Literature review current through: Nov 2016. | This topic last updated: Wed Jul 20 00:00:00 GMT+00:00 2016.
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