Makindo Medical Notes

🧬 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.