Developing spontaneous pneumothorax, folliculomas and renal tumors
Birt-Hogg-Dubé Syndrome - FLCN
Clinical Features
The clinical features of Birt-Hogg-Dubé (BHDS) include cutaneus tumours (fibrofolliculomas) typically by age 30 to 40. The skin manifestations besides the fibrofolliculomas are angiofibromas, perifollicular fibromas and papillomateus skin lesions. Additional findings are pulmonary cysts, spontaneous pneumothoraces and renal tumors. Individuals with lung cysts (mostly bilateral and multifocal) are asymptomatic, but have a high risk of developing spontaneous pneumothorax. The risk for a pneumothorax for BHDS patients is 50-fold higher compared to the normal population. Individuals have an increased risk for renal tumors, typically bilateral, multifocal and slow growing. Median age of diagnosis is 48 years (from 31 to 78 yrs). The most common renal tumors are renal oncocytoma (75%) and papillary renal carcinoma (15%), and in lower frequency, chromophobous renal carcinomas (5%) and clear cell renal (5%) Some families present renal tumours and/or autosomal dominant, spontaneous pneumothorax without skin abnormalities. Thyroid and colon carcinomas have been eliminated from tumour spectrum of Birt-Hogg-Dubé syndrome.
Genetic Information
BHDS is an autosomal dominant inherited disease. Patients have germline mutations FLCN gene. The FLCN-gene (initially BHD) is located on chromosome 16 (16q22.1) and has 14 exons. Follicullin the product of FLCN, has 579 amino acid residues. Reduced expression of folliculin in renal tumors supports its role in tumor suppression.
Diagnostic
Indication
Method
All exons of the FLCN gene as well as their flanking regions are analysed using DNA sequencing.
Deletions and/or duplications of one or more exons are captured by MLPA analysis.
Sample Requirement
2 - 4 ml of EDTA blood
Duration
2 - 3 weeks