Von Hippel-Lindau Syndrome

Clinical Characteristics
Ocular Features: 

Retinal angiomas are a feature of this syndrome, occurring in up to 70% of patients and often diagnosed by about age 25 years.  These hemangioblastomas are often connected to prominent arterioles and venules indicative of their vascular nature.  Capillary hamartomas located on or near the optic nerve may mimic papilledema or papillitis.  However, they may also occur throughout the retina and visual morbidity often results from secondary damage due to hemorrhage, exudates, and traction on the retina. When they are bilateral and multicentric the diagnosis of VHL is highly likely.  Patients with VHL tend to develop such tumors at a younger age and have worse visual outcomes than those in patients without VHL.  The impact on vision is responsible for initial presentation in many patients.

Systemic Features: 

Clinical symptoms typically have their onset during the second decade of life.  These commonly (in 35% of patients) result from the presence of a cerebellar hemangioblastoma while overall more than 60% eventually develop this malignancy.  Up to 40% of patients develop renal cell carcinomas and these are a major cause of death.   However, benign and malignant tumors may appear in many organs including the adrenal glands, pancreas, and spinal cord.  Pheochromocytomas occur in 20-35% of individuals and may be bilateral and multifocal.  These can induce an erythrocythemia. Endolymphatic sac tumors occur in about 10% of patients.  Cystic lesions are often associated with the tumors, especially in the pancreas.

Several subtypes have been proposed based on the pattern of malignancies and the types of mutations found in patients.

Genetics

This is an autosomal dominant cancer susceptibility disorder caused by a mutation in the VHL gene located at 3p26-p25.

There is evidence that the phenotype can be modified by variations in the cyclin D1 gene (CCND1) located at 11q13.

Treatment
Treatment Options: 

Local excision of isolated lesions can be considered in selected cases.  Photocoagulation and cryotherapy of retinal hamartomas can be considered although outcomes are variable depending on location and size of the lesions.

References
Article Title: 

A genetic register for von Hippel-Lindau disease

Maddock IR, Moran A, Maher ER, Teare MD, Norman A, Payne SJ, Whitehouse R, Dodd C, Lavin M, Hartley N, Super M, Evans DG. A genetic register for von Hippel-Lindau disease. J Med Genet. 1996 Feb;33(2):120-7.

PubMed ID: 
8929948

Genetic analysis of von Hippel-Lindau disease

Nordstrom-O'Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, van Brussel A, Voest EE, Giles RH. Genetic analysis of von Hippel-Lindau disease. Hum Mutat. 2010 May;31(5):521-37.

PubMed ID: 
20151405

References

Shanbhogue KP, Hoch M, Fatterpaker G, Chandarana H. von Hippel-Lindau Disease: Review of Genetics and Imaging. Radiol Clin North Am. 2016 May;54(3):409-22.

PubMedID: 27153780

McCabe CM, Flynn HW Jr, Shields CL, Shields JA, Regillo CD, McDonald HR, Berrocal MH, Gass JD, Mieler WF. Juxtapapillary capillary hemangiomas. Clinical features and visual acuity outcomes. Ophthalmology. 2000 Dec;107(12):2240-8.

PubMedID: 11097604

Maddock IR, Moran A, Maher ER, Teare MD, Norman A, Payne SJ, Whitehouse R, Dodd C, Lavin M, Hartley N, Super M, Evans DG. A genetic register for von Hippel-Lindau disease. J Med Genet. 1996 Feb;33(2):120-7.

PubMedID: 8929948

Nordstrom-O'Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, van Brussel A, Voest EE, Giles RH. Genetic analysis of von Hippel-Lindau disease. Hum Mutat. 2010 May;31(5):521-37.

PubMedID: 20151405