Von hippel-lindau syndrome Q85.8

Von Hippel-Lindau disease (VHS) is an autosomal-dominant inherited neuro-cutaneous systemic disease with nevus flammeus, various malignant and benign neoplasms, most commonly retinal, cerebellar and spinal hemangioblastomas, renal cell carcinomas (RCC) and pheochromocytomas.

Prevalence: 1-9 / 100 000

Highly penetrant mutations (mostly germline mutations) have been identified in the VHL gene (3p25.3), a classical tumour suppressor gene encoding the protein of the same name "Von Hippel-Lindau Tumor Suppressor" (pVHL). The VHL tumour suppressor protein plays a key role in cellular oxygen measurement by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation.

Infancy, childhood, adolescence, adulthood up to 7th decade of life; the mean age of diagnosis is 26 years.

Skin: nevus flammeus

Eye: Retinal hemangioblastomas are the most common first sign (multiple and bilateral in 50% of cases). They are usually asymptomatic but may cause retinal detachment, macular edema, glaucoma and loss of visual acuity.

CNS: Central nervous system (CNS) hemangioblastomas are the first symptom in about 40% of cases, and overall they occur in 60-80% of patients. They are most commonly located in the cerebellum, but also in the brainstem and spinal cord. They are benign, but cause symptoms due to pressure on adjacent nerve tissue. With tumors in the cerebellum, the most common symptoms are increased intracranial pressure, headache, vomiting, and ataxia of the limbs or trunk.

Cyst formation: Multiple renal cysts are very frequently found. Furthermore, cysts are found in the pancreas and liver.

Tumour formations in: Kidney (hypernephroma), adrenal glands(pheochromocytoma) Liver (cavernomas) and pancreas (islet cell tumors in about 10% of patients).

Other:

• Epididymal cysts and cystadenomas occur in 60% of male patients.
• Ulcers of the endolymphatic sac (ELST) are found in up to 10% of patients and may be the cause of hearing loss.
• Rare (0.5%) are paragangliomas of the head and neck. The median age of diagnosis of these tumors is considerably younger in VHL than in sporadic cases.

Considerable intrafamilial variability has been reported.

The diagnosis can be made using as little as a single typical tumor (retinal or CNS hemangioblastoma or renal cell carcinoma) and a positive family history of VHL. In the absence of a family history (approximately 20% are new mutations), the presence of multiple tumors (eg, 2 hemangioblastomas or 1 hemangioblastoma and 1 RCC) is required for diagnosis.

Imaging techniques are used to detect CNS tumors, pheochromocytoma, tumors of the endolymphatic sac, renal tumors, and renal and pancreatic cysts.

Multiple Endocrine Neoplasia (MEN)

Neurofibromatosis

Polycystic kidney disease

Tuberous sclerosis

Birt-Hogg-Dubé Syndrome

Hereditary pheochromocytoma-paraganglioma syndromes.

Interdisciplinary ophthalmological, neurological and surgical therapy approach.

1. Cushing H, Bailey P (1928) Hemangiomas of cerebellum and retina (Lindau's disease), with the report of a case. Arch Ophthal 57: 447-463
2. Lindau A (1926) Studies on cerebellar cysts. Construction, pathogenesis and relationships to angiomatosis retinae. Doctoral thesis. Acta pathologica et microbiologica Scandinavica (Copenhagen) 3 (supplement): 1-128
3. by Hippel E (1895) Presentation of a patient with a very unusual retina or choroidal disease. Report on the 24th meeting of the Ophthalmological Society in Heidelberg 24: 269