From the Guidelines
Birt-Hogg-Dubé syndrome should be managed with a multidisciplinary approach, including regular skin examinations, baseline chest imaging, and periodic kidney imaging every 1-2 years to monitor for renal tumors, as recommended by recent guidelines 1. The condition is characterized by multiple benign skin tumors, lung cysts, and an increased risk of kidney cancer, with no specific medication available to treat the underlying genetic cause.
- Key aspects of management include:
- Regular skin examinations to monitor for fibrofolliculomas
- Baseline chest imaging to detect lung cysts and prevent pneumothorax
- Periodic kidney imaging (typically MRI or CT scans) to monitor for renal tumors, which may be challenging to diagnose due to regional heterogeneity of tumors 1
- For skin lesions, treatments like laser therapy or surgical removal may be considered for cosmetic reasons, while patients with lung cysts should avoid activities that cause sudden pressure changes, such as scuba diving or flying in unpressurized aircraft.
- Family members should consider genetic testing since this condition follows an autosomal dominant inheritance pattern, meaning each child of an affected person has a 50% chance of inheriting the mutation, and the term "hybrid oncocytic tumor" has been used variably in the literature, but should be reserved for hereditary cases, which are often characterized by scattered clusters and individual cells with clear cytoplasm, exhibiting a "checkerboard" mosaic pattern (as in BHD syndrome) 1.
From the Research
Birt-Hogg-Dubé Syndrome Overview
- Birt-Hogg-Dubé syndrome is an autosomal dominant condition characterized by skin fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cancer 2.
- The syndrome is caused by germline mutations in the FLCN gene, which encodes folliculin, a protein linked to the mTOR pathway 2, 3.
- Patients with Birt-Hogg-Dubé syndrome have an increased risk of developing kidney cancer, which is often bilateral and multifocal 4, 5.
Clinical Manifestations
- The clinical expression of Birt-Hogg-Dubé syndrome typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas, and renal tumors of various histological types 5.
- Renal tumors affect about 30% of patients during their lifetime and can be multiple and recurrent 5.
- The predominant forms of Birt-Hogg-Dubé syndrome-associated renal tumors are hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma, which are typically less aggressive 3.
Diagnosis and Management
- The diagnosis of Birt-Hogg-Dubé syndrome is based on a combination of genetic, clinical, and/or skin histopathological criteria 5.
- Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumor detection, and diagnostic work-up in search of Birt-Hogg-Dubé syndrome in relatives of the index patient 5.
- Surveillance data and medical records of patients with Birt-Hogg-Dubé syndrome show that compliance to renal screening is relatively high, and ultrasound might be a sensitive, cheap, and widely available alternative for MRI or part of the MRIs for detecting clinically relevant renal tumors in BHD patients 6.
- Nephron-sparing surgery is recommended for renal tumors, and the timing of surgery is critical for postoperative renal function, which is an important prognostic factor for Birt-Hogg-Dubé syndrome patients 4, 3.