From the Guidelines
Birt-Hogg-Dubé syndrome is a rare genetic disorder that requires regular screening and management of its manifestations, including skin growths, lung cysts, and kidney tumors, with the goal of reducing morbidity, mortality, and improving quality of life. The condition is caused by mutations in the FLCN gene and is characterized by a spectrum of renal tumors with variable degrees of oncocytic differentiation, as well as skin lesions and lung cysts that can lead to pneumothorax 1. Management typically involves regular screening with imaging studies such as abdominal MRI or CT scans every 1-2 years to monitor for kidney tumors, chest imaging to assess lung cysts, and dermatological evaluation for skin manifestations.
- Key considerations in managing Birt-Hogg-Dubé syndrome include:
- Regular screening for kidney tumors, with a low threshold for FH, 2SC, and SDHB immunohistochemistry in any difficult to classify renal carcinoma, particularly in younger patients 1
- Management of skin lesions, which may include laser therapy or surgical removal
- Standard medical intervention for pneumothorax
- Surgical management of kidney tumors if detected
- Genetic counseling for affected individuals and their families, given the autosomal dominant inheritance pattern of the condition 1
- Patients with Birt-Hogg-Dubé syndrome should avoid activities that increase pressure changes in the lungs, such as scuba diving or flying in unpressurized aircraft, to reduce pneumothorax risk.
- Referral for genetic counseling should be considered for any individual with a personal history of or first-degree relative with Birt-Hogg-Dubé syndrome, particularly if they have ≥5 Birt-Hogg-Dubé-associated facial or truncal papules or early-onset (<50) renal cell tumors 1.
From the Research
Birt-Hogg-Dubé Syndrome Overview
- Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterized by diffuse pulmonary cysts, cutaneous fibrofolliculomas or trichodiscomas, and a variety of renal cell cancers 2, 3.
- The condition is caused by pathogenic variants in the FLCN gene located on chromosome 17p11.2 2, 3.
Clinical Features
- Patients with BHD syndrome can present with skin signs, pneumothorax, or renal cancer 3.
- Pulmonary cysts and pneumothorax are the main presenting features, but skin and renal lesions appear to be less common in Chinese subjects than those reported from European and American countries 2.
- Cutaneous fibrofolliculomas, lung cysts, spontaneous pneumothoraces, and parotid oncocytoma are common features among BHD patients 4.
Diagnosis and Management
- The folliculin (FLCN) gene is currently the only affirmative causative gene for BHD syndrome, and genetic testing can assist in the rapid identification of causative gene variants 2.
- Patients with BHD syndrome should undergo chest CT scan to evaluate cystic lesions in the lungs, and routine evaluation of the kidneys for tumor foci 2.
- Clinicians should establish a diagnosis based on the appropriate clinical presentation and in conjunction with genetic test results and/or a family history of BHD syndrome 2.
- A multidisciplinary approach to management is recommended, including respiratory and critical care medicine, radiology, pathology, thoracic surgery, urology, genetics, and dermatology 2, 4.
Screening and Surveillance
- Preventive measures are aimed mainly at early diagnosis and treatment of renal cancer 3.
- Annual abdominal MR examination is recommended for patients with BHD syndrome complicated by renal tumors 2.
- Routine screenings of kidney cancer during their lifetime are recommended for patients with BHD syndrome 2, 5.
- 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 tumours in BHD patients 5.
Treatment
- Surgical removal with nephron-sparing is a therapeutic principle for BHD syndrome-associated renal tumors 6.
- The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for BHD syndrome patients 6.
- Early pleurodesis is recommended to reduce the risk of recurrence in patients with BHD syndrome complicated by pneumothorax 2.