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.
They often do not cause additional morbidity but may in up to one-half of patients. Neurocognitive impairment, attention-deficit hyperactivity disorder,  autism spectrum disorder and behavioral disorders are also commonly seen in patients with neurofibromatosis type 1. Epilepsy is seen in 4-7% of patients.Musculoskeletal system manifestations can develop in patients with neurofibromatosis type 1. Common findings include sphenoid wing dysplasia, osteopenia, osteoporosis, anterior chest wall deformities as well as scoliosis. Patients are at a much greater risk for fractures than the general population.Vascular abnormalities are also frequently encountered in patients with neurofibromatosis type 1. These may include renal artery stenosis, pulmonary artery stenosis, cerebral artery stenosis and aneurysms. Complications may include myocardial infarction and stroke. Relative to the general population the risk for certain types of cancer is increased significantly. For instance, the risk for brain tumors and breast cancer is increased by 5 times. Neurofibromatosis Type II
Neurofibromatosis type 2 is an autosomal dominant condition that affects approximately 1 in 35,000-40,000 people. It is caused by mutations in the NF2 gene on chromosome 22 which has a high penetrance though most patients do not present with symptoms until adulthood. Approximately half of patients have de novo mutations and as many as 59.7% are mosaic. Patients who present in childhood tend to have a more severe phenotype.Bilateral vestibular schwannomas are the most characteristic finding and in the vast majority of cases are benign. However, they are responsible for significant morbidity and are responsible for the most common presenting symptom of hearing loss in adults.