Neurofibromatosis, type 1 & 2
Neurofibromatosis is the most common neurocutaneous disorder. The two most common types are neurofibromatosis 1 (NF1, also known as Von Recklinghausen’s Disease) and neurofibromatosis 2 (NF2). The incidence of NF1 is 1/3000 births versus 1 in 40,000 for NF2, making NF1 much more common. NF1 is associated with an abnormality of chromosome 17, while NF2 is associated with a defect of chromosome 22. Up to 50% of cases of NF1 and NF2 may be inherited in an autosomal dominant fashion.
Diagnostic criteria for NF1 are two or more of the following: ≥6 café au lait spots, ≥2 neurofibromas of any type or 1 plexiform neurofibroma, optic glioma, ≥2 Lisch nodules (pigmented iris hamartomas), distinctive osseous abnormality such as sphenoid dysplasia or thinning of long bone cortex, and a first degree relative with NF1 by this criteria. Schwannomas are associated with NF1, but bilateral vestibular schwannomas are only seen in NF2. Pheochromocytomas and intellectual impairment may also be seen in NF1. Management of optic gliomas in NF1 is usually conservative, as most rarely involve the nerve and are non-progressive. Intracranial tumors should be managed using the same criteria as in the general population.
Definitive diagnostic criteria for NF2 are as follows: bilateral vestibular schwannomas on imaging or a first degree relative with NF2 and either a unilateral vestibular schwannoma at age nd to 3rd decades of life with rapid hearing loss and multiple associated tumors. The second form is milder, presenting later in life with slower loss of hearing and fewer associated tumors. Bilateral vestibular schwannomas are best excised surgically when small in order to maximize hearing preservation. If removal of 1 tumor restores hearing, the second tumor may be observed or removed surgically as well. A subtotal resection may be undergone to avoid total deafness. Stereotactic radiosurgery is another option. Most patients will become eventually become deaf.
Hereditary Hemorrhagic Teliangiectasia (HHT, aka Osler Weber Randu)
Hereditary hemorrhagic telangiectasia (HHT, also known as Osler-Weber-Rendu syndrome) is a genetic vascular disease inherited in an autosomal dominant fashion. Capillaries become slightly enlarged with low flow. About 1 in 5,000 people are affected. Cerebrovascular malformations include telangiectasias, arteriovenous malformations (AVM, discussed separately), and venous angiomas and aneurysms. A common presenting symptom is recurrent epistaxis. Surgery is only necessary for evacuation of a hematoma or diagnosis. It also may be considered for recurrent hemorrhages or medically intractable seizures.
Foster Kennedy syndrome
This is a syndrome typically produced by olfactory groove or medial third sphenoid wing tumors, such as meningiomas. The classic triad of symptoms is ipsilateral anosmia, ipsilateral central scotoma, and contralateral papilledema. Central scotoma occurs due to optic atrophy from tumor compression of the optic nerve. Papilledema results from increased intracranial venous pressure.
Tuberous sclerosis has a prevalence of 1 in 6,000-10,000 live births. The clinical triad of symptomatic presentation is seizures, mental retardation, and sebaceous adenomas. Subependymal nodules (“tubers”), a type of hamartoma, are a common intracranial finding. Hamartomas occur throughout the entire body. Subependymal giant cell astrocytomas are also seen. There are two tumor suppressor genes that are commonly mutated, TSC1 on chromosome 9 (encoding hamartin), and TSC2 on chromosome 16 (encoding tuberlin).
Von Hippel-Lindau Disease (VHL)
This is a familial disorder presenting with hemangioblastomas of the cerebellum, retina, brainstem, and spinal cord. Pheochromocytomas and renal cysts and tumors are also commonly seen. The main genetic mutation is inactivation of a tumor suppressor gene on chromosome 3, and it is inherited in an autosomal dominant fashion. It occurs in 1 in 31,000-36,000 live births. Thirty percent of patients with cerebellar hemangioblastomas have VHL. The age of presentation is variable.
Wyburn-Mason syndrome is considered one of the nonhereditary congenital neurocutaneous disorder and is characterized by arteriovenous malformations (AVMs) of eyes and brain, typically involving the retina, visual pathways, midbrain, and facial structures. In contrast to other neurocutaneous disorders, Wyburn-Mason syndrome does not commonly cause cutaneous manifestations. Common presenting symptoms includes seizure, mental changes, hemiparesis, and papilledema, which are frequently a source of hemorrhage, unlike the hemangioma of SWS.