However, the clinical presentation can vary significantly depending on the timing of the somatic mutation ranging from an isolated port-wine stain to complete Sturge-Weber syndrome.The characteristic port-wine stain, also called nevus flammeus, is caused by a capillary or venular malformation. It is present from birth while the extent and size of it is associated with the risk of leptomeningeal and ophthalmologic involvement. The greatest risk is associated with port-wine stains that appear to involve the entire V1 distribution followed by partial V1 involvement. There is ontroversy as to whether or not the distribution of port-wine stains truly follows trigeminal nerve branches per se. Port-wine stains are most often unilateral but can be bilateral. Typically, brain and eye involvement occur on the same side as the port-wine stain. Over time, port-wine stains can develop soft tissue or bone hypertrophy, proliferative nodules, and progressive ectasia which can lead to significant disfigurement.The two most common ocular manifestations include glaucoma and choroidal hemagioma. Glaucoma is estimated to occur in 30-70% with a bimodal peak occurring at the time of birth in 60% and between childhood and adolescence in 40%. The most frequent form of glaucoma is open-angle however closed-angle glaucoma may also occur. Congenital onset glaucoma is associated with other changes of the eye including megalocornea and buphthalmos. The choroidal hemangioma occurs in 40-50% of patients.
Life expectancy is reduced for individuals with this condition and one study found a median age of death at 52 years.CNS hemangioblastomas are the cardinal feature of VHL and occur in as many as 80% of cases. The most common locations include the cerebellum, spinal cord and brainstem. These tumors are benign however they may cause significant morbidity as well as mortality due to mass effect. Tumor growth rates can be highly variable. Treatment options include resection and radiation.Retinal hemangioblastomas occur in approximately half of patients and are often the first presenting manifestation of VHL. One longitudinal study that followed patients for a mean period of 7.3 years found that in individuals with unilateral disease 100% had bilateral involvement by the age of 56 years. Blindness or severe visual impairment occurs in less than 10% of patients. Laser photocoagulation and cryotherapy are the most common surgical treatments.Renal cell carcinoma is a major cause of death in patients with VHL and it occurs in 70% of patients. Lesions larger than 3 cm are associated with a risk of metastasis and thus present a recommended threshold for resection. Nephron sparing surgery allows for preservation of kidney function and 10-year survival rates up to 81%.Additional manifestations of VHL may include pheochromocytomas in as many as 16% of patients with VHL. They are most often unilateral but can be bilateral or multifocal. Approximately 5% are malignant.Pancreatic involvement occurs in 77% of patients with VHL. Asymptomatic cysts consist of the majority of cases. Neuroendocrine tumors occur in approximately 15% of cases.