What is Brittle Hogg Dube syndrome (BHD syndrome)?

From the Guidelines

Birt-Hogg-Dubé syndrome is a rare genetic disorder caused by mutations in the FLCN gene, characterized by skin lesions, bilateral and multifocal renal tumors, and multiple bilateral lung cysts often associated with spontaneous pneumothorax. This condition primarily affects the skin, lungs, and kidneys, with symptoms typically developing in adulthood 1. The key features of Birt-Hogg-Dubé syndrome include:

• Classic skin lesions such as fibrofolliculomas, perifollicular fibromas, trichodiscomas or angiofibromas, and acrochordons
• Bilateral and multifocal renal tumors, including chromophobe clear cell renal carcinoma, renal oncocytoma, oncocytic hybrid tumor, and less often, clear cell renal carcinoma
• Multiple bilateral lung cysts often associated with spontaneous pneumothorax, as reported in the study published in Genetics in Medicine in 2015 1

Management of Birt-Hogg-Dubé syndrome includes regular skin examinations, lung imaging to monitor for cysts, and kidney surveillance with MRI or CT scans every 1-3 years beginning at age 20, as well as genetic counseling for family members 1. It is essential to prioritize these measures to minimize morbidity, mortality, and improve quality of life for individuals with this condition. Regular monitoring and early detection of potential complications are crucial in managing Birt-Hogg-Dubé syndrome, and the guidelines provided by the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors should be followed 1.

From the Research

Definition and Characteristics of Birt-Hogg-Dubé Syndrome

• Birt-Hogg-Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumor suppressor gene FLCN, encoding the protein folliculin 2.
• The clinical manifestations of BHD include multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas, and renal tumors of various histological types 2, 3.
• BHD has no sex predilection and tends to manifest in the third or fourth decade of life 2.

Clinical Features and Diagnosis

• Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients, and more than half experience one or more episodes of pneumothorax 2.
• A family history of pneumothorax is an important clue that suggests the diagnosis of BHD 2.
• The diagnosis of BHD is based on a combination of genetic, clinical, and/or skin histopathological criteria 2, 3.
• Lung histopathological biopsy is not recommended as the first choice for patients with suspected BHD syndrome based on clinical and pulmonary imaging manifestations 3.

Management and Treatment

• Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumor detection, and diagnostic work-up in search of BHD in relatives of the index patient 2.
• Patients with BHD syndrome should avoid smoking and are recommended to be vaccinated with influenza, pneumococcal, and SARS-Cov-2 vaccines to prevent infections 3.
• Air travel is not recommended for patients with BHD syndrome who have experienced pneumothorax until it has been recovered 3.
• Observation or topical treatment may be chosen for patients with BHD syndrome complicated by fibrofolliculoma or trichodiscoma 3.

Genetic Aspects and Family Management

• The folliculin (FLCN) gene is currently the only affirmative causative gene for Birt-Hogg-Dubé (BHD) syndrome, and pedigree analysis of genetic testing of family members' samples can assist in the rapid identification of causative gene variants 3.
• Family members of patients with BHD syndrome should receive health education, and FLCN gene testing is recommended for asymptomatic adults to rule out BHD syndrome in a timely manner 3.
• Couples with BHD syndrome are advised to undergo prenatal genetic counseling when preparing for pregnancy, to work with a prenatal diagnostician to assess genetic risk, and to discuss the feasibility of prenatal diagnosis during pregnancy 3.