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. they are usually asymptomatic but they may become thickened overtime and may be associated with an increased risk for glaucoma. seizures typically develop within the first two years of life and occur in 75-100% of patients. onset of seizures occur in 95% by the age of 5 years. status epilepticus occurs in approximately 50% of patients. approximately 25% of patients develop drug-resistant epilepsy. in these cases, surgery may be pursued with the two main approaches being lesionectomy and hemispherectomy. neurological impairment can accrue gradually over time and may occur in the context of stroke-like episodes which may be triggered by seizures or head injuries. intellectual disability occurs in approximately one-half of patients. in addition, patients with sturge-weber syndrome have an increased prevalence of depression, endocrinological abnormalities, headaches with migraine-like features, adhd and behavioral problems. cortically mediated visual field defects and hemiparesis occur in approximately one-third and one-half of patients, respectively. von hippel–lindau syndrome (hemangiomatosis) von hippel-lindau (vhl) disease is an autosomal dominant condition caused by mutations of the vhl gene. approximately one-in-five cases are de novo rather than familial and it has nearly complete penetrance. vhl occurs in an estimated 1 in 36,000-45,000 live births. vhl normally functions as a tumor suppressor gene and thus when not functioning normally results in the development of benign and malignant tumors as well as cysts. some of the most common manifestations include hemangioblastomas in the retina and central nervous system, clear cell renal cell carcinomas, pheochromocytomas, endolymphatic sac tumors and pancreatic neuroendocrine tumors. 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. less than 10% with neuroendocrine tumors will develop metastases. genetics the majority of neurocutaneous syndromes are single-gene disorders however they are caused by different genes and have different inheritance patterns. for instance, neurofibromatosis 1 and 2, tuberous sclerosis complex, von hippel-lindau syndrome and legius syndrome are inherited in an autosomal dominant manner. incontinentia pigmenti is x-linked dominant and sturge-weber syndrome is sporadic. some neurocutaneous disorders are found exclusively as mosaics such as sturge-weber syndrome and proteus syndrome. others such as neurofibromatosis type 1 and 2 as well as tuberous sclerosis complex can potentially be mosaics but may not be. mosaicism may be suspected in cases with either a mild or incomplete presentation of a neurocutaneous disorder. a definitive diagnosis is most likely to be obtained if testing of affected tissues is possible. patients and families of those affected by neurocutaneous disorders often benefit from genetic counseling. it may provide an opportunity to provide a better understanding of the potential risk to future offspring as well as to improve coping with the various implications of the condition. if desired, a prenatal diagnosis can be obtained by either amniocentesis or chorionic villus sampling. another potential option is preimplantation genetic diagnosis where an embryo that does not have the mutation can be selectively implanted into the mother. diagnosis many neurocutaneous syndromes have established diagnostic criteria which may facilitate a diagnosis without necessarily requiring genetic testing. for instance, neurofibromatosis types 1 and 2, tuberous sclerosis complex and incontinentia pigmenti have formal diagnostic criteria. whereas other syndromes such as noonan syndrome with multiple lentigines, for instance, do not. in cases where conditions that do not have diagnostic criteria are suspected, genetic testing is more likely to be necessary. diagnostic criteria are not perfect as sensitivity and specificity is not 100%. similarly, genetic testing can produce false negatives. for example, genetic testing is positive in only 75-90% of cases of tuberous sclerosis complex. thus, clinicians must apply clinical judgement when evaluating an individual suspected to have a neurocutaneous syndrome. treatment the treatment of each neurocutaneous syndrome is unique. for some neurocutaneous syndromes such as neurofibromatosis 1 and tuberous sclerosis complex there are guidelines with recommendations for surveillance and management. for less common syndromes such guidelines are not yet available. surveillance is a necessity for many neurocutaneous syndromes because new manifestations may develop over time which may only be detected with specific and focused testing. thus, patients may be advised to obtain particular evaluations (e.g., mri, ophthalmologic or dermatological examinations) within recommended intervals over time with the aim of detecting new manifestations of the syndrome early on. most of the currently available treatments for neurocutaneous syndromes do not address the underlying genetic cause. for example, epilepsy surgery in tuberous sclerosis complex or vestibular schwannoma surgery in neurofibromatosis type 2. however, there are some treatments that do address the underlying cause such as the use of mtor inhibitors in tuberous sclerosis complex. there are currently significant efforts underway to develop additional treatments that address the underlying causes of neurocutaneous syndromes. neurocutaneous syndromes are complex, lifelong conditions that have the potential to affect many different organ systems over time. thus, patients may benefit from a multidisciplinary approach for care. integrated, multidisciplinary clinics have developed in an effort to optimize the long-term care for patients with neurocutaneous syndromes. specialties represented at these clinics may include genetics, neurology, ophthalmology, hematology-oncology, neurosurgery, psychiatry, dermatology and more.