Von Hippel-Lindau (vHL) disease is characterised by the development of numerous benign and malignant tumours in different organs (at least 40 types 1) due to mutations in the VHL tumour suppressor gene on chromosome 3.
The disease is rare with an estimated prevalence of 1:35,000-50,000.
Clinical presentation is varied, depending on the site of disease manifestation (see below). Most commonly these are either within the abdominal cavity or central nervous system.
Patients may develop some or all of the various lesions which include:
- renal lesions
- numerous pancreatic lesions (may be the earliest manifestation 3)
- liver cysts
- papillary cystadenoma(s) of the epididymis
- paraganglioma (rare) 8
Head and neck
- most common presenting feature 9
- vision loss in 35-55% of patients 9
endolymphatic sac tumours (ELST)
- bilateral ELSTs considered pathognomonic for vHL 9
Features can be remembered by the mnemonic HIPPEL:
- Increased risk of RCC
- Pancreatic lesions (cysts, cystadenomas, cystadenocarcinomas)
- Eye dysfunction (retinal haemangioblastomas)
- Liver, renal and pancreatic cysts
The disease carries an autosomal dominant inheritance with high expression and variable penetrance. It classically results from an inactivation of VHL, a tumour suppressor gene located on chromosome 3p25.5. However, no mutation is identified in up to 30% of cases.
Please refer to articles on individual lesions for specific imaging characteristics.
Treatment and prognosis
Most lesions from vHL are treatable and screening is recommended. Some experts advocate routine screening starting in adolescence. Prognosis is poor, with a median survival of ~50 years, with the most common cause of death being RCC and cerebellar haemangioblastomas 1.
History and etymology
Eugen von Hippel (1867-1939) was a German ophthalmologist who had described a rare disorder of the retina in 1904 and seven years later reported the basis of this disease, named as "angiomatosis of the retina".
Arvid Vilhelm Lindau (1892-1958) was a Swedish pathologist and bacteriologist who described the association between angiomatosis of the retina and haemangioblastomas of the cerebellum and other parts of the CNS and other visceral components of a disease, calling it "angiomatosis of the central nervous system".
In 1964 the disease was renamed Von Hippel-Lindau disease.
- 1. Leung RS, Biswas SV, Duncan M et-al. Imaging features of von Hippel-Lindau disease. Radiographics. 28 (1): 65-79. doi:10.1148/rg.281075052 - Pubmed citation
- 2. Marcos HB, Libutti SK, Alexander HR et-al. Neuroendocrine tumors of the pancreas in von Hippel-Lindau disease: spectrum of appearances at CT and MR imaging with histopathologic comparison. Radiology. 2002;225 (3): 751-8. doi:10.1148/radiol.2253011297 - Pubmed citation
- 3. Hough DM, Stephens DH, Johnson CD et-al. Pancreatic lesions in von Hippel-Lindau disease: prevalence, clinical significance, and CT findings. AJR Am J Roentgenol. 1994;162 (5): 1091-4. AJR Am J Roentgenol (abstract) - Pubmed citation
- 4. Courcoutsakis NA, Prassopoulos PK, Patronas NJ. Aggressive leptomeningeal hemangioblastomatosis of the central nervous system in a patient with von Hippel-Lindau disease. AJNR Am J Neuroradiol. 2009;30 (4): 758-60. doi:10.3174/ajnr.A1360 - Pubmed citation
- 5. Taouli B, Ghouadni M, Corréas JM et-al. Spectrum of abdominal imaging findings in von Hippel-Lindau disease. AJR Am J Roentgenol. 2003;181 (4): 1049-54. AJR Am J Roentgenol (full text) - Pubmed citation
- 6. Choyke PL, Glenn GM, Walther MM et-al. von Hippel-Lindau disease: genetic, clinical, and imaging features. Radiology. 1995;194 (3): 629-42. Radiology (abstract) - Pubmed citation
- 7. Bodmer D, Van den hurk W, Van groningen JJ et-al. Understanding familial and non-familial renal cell cancer. Hum. Mol. Genet. 2002;11 (20): 2489-98. doi:10.1093/hmg/11.20.2489 - Pubmed citation
- 8. Gaal J, van Nederveen FH, Erlic Z et-al. Parasympathetic paragangliomas are part of the Von Hippel-Lindau syndrome. J. Clin. Endocrinol. Metab. 2009;94 (11): 4367-71. doi:10.1210/jc.2009-1479 - Pubmed citation
- 9. Maher ER, Neumann HP, Richard S. von Hippel-Lindau disease: a clinical and scientific review. Eur. J. Hum. Genet.19 (6): 617-23. doi:doi:10.1038/ejhg.2010.175 - Free text at pubmed - Pubmed citation
- neurofibromatosis type 1 (NF1) (von Recklinghausen disease)
- neurofibromatosis type 2 (NF2) (mnemonic)
- tuberous sclerosis (Bourneville-Pringle disease)
- ataxia telangiectasia
- Sturge-Weber syndrome (encephalotrigeminal angiomatosis)
- von Hippel-Lindau disease (retinocerebellar angiomatosis)
- incontinentia pigmenti (Bloch-Sulzberger syndrome)
- basal cell naevus syndrome (Gorlin-Goltz syndrome)
- Wyburn-Mason syndrome (Bonnet-Dechaume-Blanc syndrome)
- encephalocraniocutaneous lipomatosis
- hypomelanosis of Ito
- Nijmegen breakage syndrome
- epidermal naevus syndrome
- neurocutaneous melanosis
- progressive facial hemiatrophy (Parry-Romberg syndrome)
- PHACE syndrome
- Cowden disease/COLD syndrome
- Gomez-Lopez-Hernandez syndrome