Makindo Medical Notes

🧬 Von Hippel-Lindau (VHL) disease is an autosomal dominant tumour syndrome. ⚠️ Renal cell carcinoma is the leading cause of death. Other hallmark features: 🎯 retinal, cerebellar, and spinal haemangioblastomas.

📌 About Von Hippel-Lindau Disease

• Rare genetic disorder → predisposes to multiple benign and malignant tumours.
• Most commonly affects: 🧠 CNS, 👁️ retina, 🩺 kidney, 🥼 adrenal glands, and pancreas.
• Prevalence: ~1 in 36,000 worldwide.

🧬 Aetiology

• Mutation in the VHL gene (chromosome 3p25-26) – tumour suppressor gene.
• VHL protein normally regulates hypoxia-inducible factors (HIFs). 👉 Mutation → uncontrolled angiogenesis & tumour growth.
• Autosomal dominant inheritance, 50% transmission risk to offspring.

🩺 Clinical Features

• Polycythaemia: From EPO secretion by haemangioblastomas → ↑ Hb/Hct.
• Renal Cell Carcinoma (RCC): Leading cause of death; haematuria, loin pain, palpable mass.
• Phaeochromocytomas: Hypertension, palpitations, sweating due to catecholamine excess.
• Multiple Cysts: Kidney, pancreas, and liver – often asymptomatic.
• CNS Haemangioblastomas: Headaches, ataxia, weakness (cerebellar/brainstem/spinal lesions).
• Retinal Haemangioblastomas: Visual loss if untreated; visible on fundoscopy.

🔬 Investigations

• Bloods: FBC (polycythaemia), plasma metanephrines/catecholamines if suspect phaeochromocytoma.
• MRI (with gadolinium): Gold standard for CNS haemangioblastomas.
• Ultrasound/CT Abdomen: For renal masses, pancreatic and hepatic cysts.
• Urinalysis: Microscopic haematuria → possible RCC.
• Genetic Testing: Confirms diagnosis, enables screening in relatives.

💊 Management

• Surveillance: Lifelong → annual/biannual MRI brain & spine, abdominal imaging, retinal exams.
• Renal Tumours: Nephron-sparing surgery preferred. Larger lesions → partial/total nephrectomy.
• Phaeochromocytomas: Surgical excision after α- then β-blockade.
• Retinal Haemangioblastomas: Laser photocoagulation or cryotherapy to preserve vision.
• CNS Lesions: Neurosurgical resection for symptomatic haemangioblastomas.
• Genetic Counselling: Vital for family planning and screening relatives.

📉 Prognosis

• Depends on early detection and treatment of RCC and CNS tumours.
• Mortality mainly due to metastatic renal carcinoma or complications of CNS haemangioblastomas.

📚 References

• Maher ER, et al. Von Hippel–Lindau disease: a clinical and scientific review. Eur J Hum Genet. 2011.
• NICE. (2020). Renal cancer: diagnosis and management.
• RCOphth. Ocular manifestations of systemic disease.