Birt-Hogg-Dubé Syndrome (BHDS)
What is Birt-Hogg-Dubé Syndrome?
Birt-Hogg-Dubé syndrome is a rare genetic disorder (1/100.000 individuals) that increases the risk of multiple benign (non-cancerous) and malign (cancerous) tumours in young adults and adults, with different manifestations and severity. Affected individuals can develop:
- -Benign skin tumours: particularly on the face, neck and upper chest that appear around 20-30 years of age and become larger and more numerous over time.
- Pulmonary manifestations: 89% of subjects have bilateral and multiple cysts in the lungs and 25% develop one or more pneumothoraces (abnormal accumulation of air in the chest cavity that may result in the collapse of a lung).
- Benign and malign (cancerous) kidney tumours: individuals are at a sevenfold increased risk for renal tumours. Typically these tumours are bilateral, multifocal, generally slow growing and appear around 40-50 years of age.
What causes BHDS?
BHDS is diagnosed by clinical manifestations and mutations in one of the two copies of the FLCN gene (also known as BHD gene). Some individuals (7-9%) fulfill clinical criteria but do not have an identifiable FLCN mutation.
How is BHDS inherited?
BHDS caused by FLCN gene mutations is inherited within families in an autosomal dominant way, which means that each child of an affected person has a 50% chance to inherit their FLCN mutation and develop the disease. Inheritance pattern in individuals without gene mutation is unknown, thus clinical screening is also recommended for their children affected with clinical manifestations.
What are the surveillance options for BHDS?
Individuals at risk should be followed in genetic counselling units with:
- Periodically dermatologic examination and punch biopsy of suspected cutaneous lesions. Treatment of cutaneous lesions for cosmetic purposes can be offered, even though relapse can occur
- Baseline CT of the chest at diagnosis is highly recommended for visualization and localisation of pulmonary cysts. If symptoms of pneumothorax appear, an x-ray or CT of the chest has to be immediately done and treatment should be applied.
- Baseline abdominal / pelvic CT scan or MRI at 20-25 years for visualization of renal tumours. Follow-up can be done yearly with ultrasound or biannually with MRI
- Discourage smoking, scuba diving and alpinism
Clinical practice guideline