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New Treatments for Neurofibromatosis and Neurocutaneous Disorders

Neurofibromatosis is very common. It is autosomal dominant with frequent new mutations, and perhaps the reason why we see so many frequent cases of this is that gene for NF1, so-called neurofibroma, is a huge gene. The features are cafť-au-lait spots and axillary freckles. Neurofibromas, optic gliomas, Lisch nodules can have osseous lesions; they can have hypoplastic wings of the sphenoid bone. You are also familiar with the complications: epilepsy, CNS neoplasms, rarely sarcomas, pseudoarthroses which we see occasionally.

There are diagnostic criteria for NF2 as well but you only need one of them. Bilateral acoustic neuromas certainly fit the bill. Positive family history is also helpful, and you have to add something else to that.

Tuberous sclerosis occurs in about 1:25,000 individuals. Most are new mutations, for some reason. There are many different cutaneous manifestations. Fibromas under the fingernails, epilepsy is common. Mild mental retardation, intracranial calcifications, cardiac rhabdomyomas. There are two different genes for TS so it is genetically heterogenous.

Von Hippel-Lindau occurs in about 1:40,000 individuals. It is also autosomal dominant and these are the hallmark features. Retinal angiomas, cerebral hemangioblastoma. You can see hemangiomas along the spinal cord as well. Renal cell carcinomas.

This is the presentation of von Hippel-Lindau. Most of the patientís first symptoms are retinal angiomas, and about half the patients will have them in their early 20s.

Sturge-Weber, thatís right. This is uncommon. Itís sporadic. So this is not inherited. Just because this is a lecture on genetic disorders doesnít mean that all these conditions are inherited. This is sporadic. These patients present with port wine stain in the distribution of the ophthalmic branch of the trigeminal nerve. The proper term here is " port wine stain."

Albinism is relatively common, about 1:20,000, and most cases are autosomal recessive. There are some cases which are X-linked. There are some features which are common to all patients with albinism, and obviously this is decreased skin and hair pigment. All these patients have nystagmus and they have decreased iridic pigment as well, and decreased retinal pigment which leads to their visual defect. They all have foveal hypoplasia.

This is the classification of albinism, and itís really sort of academic. It doesnít make much difference in how you manage these patients. So the big category is for oculocutaneous albinism whether or not tyrosinase is present. You can assay tyrosinase by measuring the activity biochemically in a hair bulb. So you can pluck a few hairs and send them off to some laboratory in Minnesota and a few years later the results will come back. And it really doesnít make any difference in patient management. I guess if it is tyrosinase-negative then you know that this is autosomal recessive and you can counsel the family a little more completely, but it really doesnít make a damn bit of difference in managing these patients. So there are tyrosinase-negative and tyrosinase not quite negative but deficient, and these are split up into various sub-categories. Then pure ocular albinism is both X-linked recessive and autosomal recessive.