Birt-Hogg-Dubé Syndrome
🧬 Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genetic disorder, first described in 1977 by Canadian dermatologists Arthur Birt, Georgina Hogg, and William Dubé.
It is characterised by a triad of:
🌱 Cutaneous lesions (fibrofolliculomas, skin tags, papules)
🫁 Pulmonary cysts & pneumothorax risk
🧷 Renal tumours (hybrid oncocytic/chromophobe most common)
Worldwide but underdiagnosed, it usually presents in adults, with features becoming more apparent with age.
🧬 Aetiology
- Caused by mutations in the FLCN gene (chromosome 17p11.2), which encodes folliculin.
- Folliculin functions in:
- 📈 Cell cycle regulation
- ⚡ mTOR signalling pathway (growth/metabolism)
- 🛡️ Cellular stress response
- Mutations → abnormal cell growth and differentiation → cutaneous lesions, lung cysts, renal tumours.
- Inheritance: Autosomal dominant → 50% chance of passing mutation to offspring.
🧾 Clinical Characteristics
- 🌱 Skin lesions: Fibrofolliculomas, acrochordons (skin tags), angiofibromas, oral papules, collagenomas, epidermal cysts.
- 🫁 Pulmonary cysts: Bilateral, multifocal, usually asymptomatic but predispose to spontaneous pneumothorax.
- 🧷 Renal tumours: 7x increased risk, often bilateral/multifocal, median diagnosis age ~48 years.
Most common = hybrid oncocytic/chromophobe tumours, but clear cell and papillary types also reported.
- 📉 Variable severity even within families; some may lack skin lesions but present with renal or pulmonary disease.
📋 Diagnostic Criteria
- One major criterion: ≥5 fibrofolliculomas (≥1 histologically confirmed) OR identification of a pathogenic FLCN variant.
- Two minor criteria:
- Renal cell carcinoma before age 50
- Multifocal/bilateral renal cell carcinoma
- Renal tumour with mixed chromophobe/oncocytic histology
- Multiple lung cysts ± pneumothorax
- First-degree relative with BHDS
🛠️ Management
- 🌱 Skin: Surgical/laser excision of fibrofolliculomas, but recurrence is common.
- 🫁 Lung/pneumothorax: Managed as per general population; preventive pleurodesis sometimes considered for recurrent pneumothorax.
- 🧷 Renal tumours: Nephron-sparing surgery preferred to preserve renal function; monitor growth closely.
- 🚫 Avoid: Smoking, scuba diving/high ambient pressure environments, and unnecessary radiation exposure.
👀 Surveillance
- 🩺 Dermatology: Full-body skin exam every 6–12 months (melanoma risk noted in some cases).
- 🧲 Imaging: Annual abdominal/pelvic MRI (preferred) or contrast CT for renal surveillance.
- 🦠 ENT/Endocrine: Annual parotid review & thyroid ultrasound.
- 🧪 Gastrointestinal: Colonoscopy at age 40 (earlier if family history of colorectal cancer <40).
- 🧬 Genetic testing: FLCN variant analysis for at-risk relatives → prevents unnecessary screening in non-carriers.
- 👨👩👧 Genetic counselling: Explains inheritance, reproductive options (prenatal or preimplantation genetic testing possible).
📌 Summary
Birt-Hogg-Dubé syndrome = triad of skin, lung, and renal manifestations caused by FLCN mutation.
Early recognition is vital due to the renal cancer risk.
Management is multidisciplinary: dermatology, respiratory, nephrology, genetics.
🧬 Genetic testing & family counselling are key for prevention and early intervention.
