Von Hippel-Lindau (VHL) disease is a rare autosomal dominant genetic disorder with incomplete penetrance and variable expression, which is associated with the lifelong risk of development of malignant and benign tumours in the central nervous system (CNS) and viscera [1,6].

This syndrome belongs to the phakomatoses and is caused by highly penetrant mutations in the VHL tumour suppressor gene on the short arm of chromosome 3p25-26 [6,15,30]. Beside 20% de novo mutations, most cases are diagnosed by a germline mutation [6]. The protein encoded by this gene is involved in the ubiquitination and degradation of a hypoxia-inducible factor (HIF). Its dysregulation can lead to increased expression of tumour promoter proteins such as the vascular endothelial growth factor, e.g., which in turn leads to tumour development [1].

Depending on the type of mutation as well as an association with pheochromocytoma, two types of the familial disease are distinct. Type 1 VHL disease may present with retinal angioma, CNS haemangioblastoma, renal cell carcinoma (RCC), pancreatic cysts and neuroendocrine tumours, but carries a low risk of pheochromocytoma. Type 2 VHL disease is characterised by a high risk of pheochromocytoma. The latter one is furthermore classified

in Type 2A (haemangioblastoma and pheochromocytoma with low risk of RCC), Type 2B (haemangioblastoma, pheochromocytoma and RCC) and Type 2C (pheochromocytoma as only manifestation). Data of the disease’s prevalence vary depending on particular regions between 1:35,000 – 91,000 [6,7,8,20,25,29]. The incidence is reported to range between 1:35,000 – 65,000 live births, whereby the incidence between the sexes appears to be similar [1,5,10,15,20,29]. Contrary to the overall population, the life expectancy is higher in men (59 years) than in women (48 years) [7]. There are no reports in the literature of demonstrable VHL features in foetal or neonatal life [1,9,26]. Clinical symptoms develop on average in the third to fourth decade of life [1,6,10]. Symptoms of VHL vary among patients, depending on size and location of the tumours and their clinical presentation. Especially in the CNS, the tumour reflects its mass effect [20,25]. Headaches, seizures, ataxia, gait imbalance, limb weakness, paraplegia, spasticity, numbness, dizziness, behavioural abnormalities, an altered mental status, progressive neurological impairment, visual impairment up to blindness, hearing loss, tinnitus, vertigo, palpitation, polycythaemia (due to erythropoietin production by cerebellar haemangioblastomas), fever, drenching sweats, vomiting, severe hypertension and acute abdomen arising from pancreatic cystadenoma have been reported [1,2,6,8,9,13,14,15,25,26,29]. Patients frequently have asymptomatic spinal cord and intracranial pathology as well as abdominal tumours, but nevertheless VHL disease may even lead to death [18,28]. The most common causes of death are complications associated  with RCC and CNS haemangioblastomas [1]. Patients are also prone to the risk of unnecessary and extensive surgery with serious consequences in the long run, i.e. nephrectomy up to haemodialysis [29]. Generally, this complex multisystem disease requires input from multiple specialists to avoid preventable morbidity and mortality [1]. The mainly associated tumour entity in the CNS is the haemangioblastoma, which is a benign vascular tumour. It is commonly located in the cerebellum, brainstem, spinal cord, retina and nerve roots [1]. Its location in the supratentorial region or the endolymphatic sac of the middle ear is rare [1,29]. Visceral features of the disorder include renal cysts and renal cell carcinoma, pheochromocytomas, pancreatic cysts and neuroendocrine tumours, liver tumours as well as epididymal and broad ligament cystadenomas [1,6,15].

Definitive diagnosis is done by imaging in addition to genetic panel and testing of the VHL gene [1,6]. Computerised axial tomography scanning (CT), magnetic resonance imaging (MRI) and angiography are the imaging techniques of choice [8,28]. Ultrasonography of abdomen, ophthalmologic fundus examination, laboratory examination (i.e., raised vanillylmandelic acid or metanephrine in urine or plasma) as well as family history for cerebellar or retinal haemangioblastoma are of significant value, too [5,18,25]. VHL patients are recommended to undergo surveillance with the aim of early detection of asymptomatic manifestations. This strategy is considered essential to plan the most optimal treatment strategy to best prevent severe sequelae such as blindness, neurological damage and early death. There is no systemic treatment for VHL [19]. Therapeutic options include surgical resection of accessible lesions and focused high-dose radiation [25]. Tumours are often not removed before they become symptomatic [19]. Nevertheless, there is a recurrent risk after an apparently complete excision of a haemangioblastoma [9]. In case of pheochromocytoma, α-blockade with prazosin and a β-blocker is useful in the management of blood pressure control [6,12,25].