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.
They can also less commonly present with dizziness or balance impairment. It is estimated that schwannomas occur in over 90% of patients.Meningiomas are the second most common tumor in NF2. Approximately half of patients have an intracranial meningioma and extramedullary spinal meningiomas occur in one-fifth of patients. Relative to the general population, meningiomas in NF2 tend to occur at a younger age, are more likely to be multiple and are associated with increased mortality.Spinal cord ependymomas occur in 20-50% of patients but they are asymptomatic in the majority of cases. In cases that they are symptomatic the specific presentation will depend upon where they are located. Potential symptoms include back pain, weakness and sensory changes. Peripheral neuropathy eventually occurs in most patients with NF2. In some cases, a mononeuropathy affecting the facial nerve can occur as the first presenting symptom of NF2. Other potential manifestations include focal amyotrophy, mononeuropathy multiplex or a severe generalized polyneuropathy in 3-5% of patients.Ophthalmologic manifestations are also common with 60-80% of patients developing cataracts. Optic nerve meningiomas and retinal hamartomas can result in vision loss. Approximately, 70% of patients will have cutaneous manifestations but only 10% have more than 10 lesions. The majority of skin lesions are schwannomas but neurofibromas can also occur. Tuberous sclerosis (Bourneville syndrome)
Tuberous sclerosis complex (TSC) is a multisystemic disorder due to autosomal dominant mutations in either TSC1 or TSC2 which results in the impaired inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway.