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RAS pathway and disease: neurofibromatosis and beyond
Published on September 3, 2014 45 min
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Hello. My name is Eric Legius. I'm a human genetics professor at University of Leuven, and I want to introduce you in the interesting world of neurofibromatosis type one and the rasopathies.
Neurofibromatosis step one is a genetic disorder with an autosomal dominant inheritance pattern. Its gene is known, and it's localized on chromosome 17, band q11.2. The prevalence at birth is one 2,700. It is considered to be a familial tumour syndrome. On the other hand, cognitive problems such as learning disabilities are also very frequently observed in children. The diagnosis is based on clinical criteria.
In 1988, an NIH panel has made diagnostic criteria for the clinical diagnosis of neurofibromatosis type one. On this slide, all the different criteria are listed, and two or more of these criteria have to be fulfilled to make a clinical diagnosis of neurofibromatosis type one. And on the next slide, we will show several of these clinical features.
On this slide, we see seven different images. They all represent different criteria for the clinical diagnosis of neurofibromatosis type one. The left upper image shows you the multiple cafe-au-lait spots that can be seen on the skin of individuals with neurofibromatosis type one. They're usually present in the first year of life. The upper middle image shows us axillary freckling. Axillary freckling represents small pigmented dots in the axilla. The same type of freckling can also seen in the inguinal region. The right upper image shows cutaneous neurofibromas. We see the left upper arm of an individual with neurofibromatosis type one, and we see three different cutaneous neurofibromas. Some of these cutaneous neurofibromas have overlying skin which is slightly violet in color. And this is typically seen in these cutaneous neurofibromas. When we go to the lower panel of this slide, on the left side we see the right upper arm of an individual with NF1 with a very large hyper pigment region. And this region also shows hypertrichosis Under this region with hyperpigmentation and hypertrichosis, there is a plexiform neurofibroma which is a larger tumor consisting of several nerves and nerve branches. If you palpate this region, you will feel a mixture of soft and hard tissues and nodules. And some of these nodules might be painful to the touch. In the middle part of this slide, we see the iris of the eye. And in the iris of the eye, we see small pigmented regions in globs. And these are globs or nodules of melanocyte. These nodules are called Lisch nodules and are very specific and typically seen in neurofibromatosis type one. Under the iris, we see the CT scan of the brain, which is focused on the eyes and the optic nerves. And one of the optic nerves is greatly enlarged and shows an optic pathway glioma. On the right lower side, we see the lower limb of an individual with NF1. And we see that the tibia is bent. And at the position where the tibia is bent, we see a small cyst and a fracture. This represents tibial pseudarthrosis.