Neurofibromatosis (NF) aka “ von Recklinghausen disease ”

1. Neurofibromatosis (NF)aka “von Recklinghausen disease” Brennan Coffey Logan Ernst Period 3

2. What is it? • Neurofibromatosis is a class of genetic disorders that causes tumors to grow in the nervous systemcalled neurofibromatoses • The process begins in the myelin sheath that coats the nerve cell • it causes a transformation that eventually leads to the growth of tumors that cause other disorders that can be seen in abnormalities such as skin changes and bone deformities

3. What is it? • The disorder is most commonly inherited, however there is a chance that a mutation could develop and cause the disorder to arise • nearly 30-50% of new cases arise out of random mutation, not genetic inheritance • There are currently 3 different types of NF, they are NF type 1, NF type 2 and schwannomatosis which used to be classified as a type of NF2, but is more appropriately its own class

5. What is it?NF1 • To diagnose NF, a doctor would look at • skin appearance • bone abnormalities • Tumors • in addition to this they would also consider the predisposition to the disease as is indicated by family history

6. What is it?NF1 • Many of the color abnormalities are evident as light brown spots on the skin • two or more growths on the iris a tumor on the optic nerve • an abnormal head circumference, abnormal developments of the spine, skull bone or tibia • Symptoms for NF1 are generally mild and those who suffer from it live normal and productive lives, however there is a possibility NF1 is severely debilitating and has cosmetic and physiological repercussions

8. What is it?NF2 • The difference between NF2 and NF1 is the fact that NF2 has slower-growing tumors • To diagnose NF2 doctors would look at the eighth nerve tumors, development of cataracts at an early age, or other nervous system tumors and the relative growth of the tumors

9. What is it?Schwannomatosis • Schwannomatosis is characterized as being comprised of different cells than other tumors (schwannomas) • It is named for Theodor Schwann, a German physiologist who is best known for his theory that all animals consist of cells • As these tumors cause pressure to neighboring nerves, a very common symptom in diagnosis is pain as the nerve develops and compresses nearby tissues

10. What is it?Schwannomatosis • With NF2 and schwannomatosis there is more danger as the cancer can grow to damage nearby tissues such as cranial or cardiac tissues which can have fatal corollaries in addition to great pain

11. Inheritance • The disease is autosomal dominant, meaning that it affects both sexes equally • It is not co-dominant so the only genotypes that correspond with the disorder are RR, Rr and rr, the homozygous recessive pair codes for not having the disorder

13. Inheritance • NF1 has a frequency of 1 in 3,000 and NF2 has a frequency of 1 in 45,000 and Schwannomatosis has a frequency of 1 in 40,000 • If a parent has NF, there is a 50-100% chance that the child will inherit the trait • There is no specific phenotype expression of the gene, as it varies between each case, however there is a similar correlation in the expression within the same family

14. Autosomal Dominant Inheritance Table

15. TreatmentNF1 • Some NF1 tumors can become cancerous so the best and most immediate solution that is recommended is surgery to remove the tumors before they can mastasize or cause damage in another fashion • As an alternative, other cancer treatment options are also viable, such as chemotherapy and radiation

17. TreatmentNF2 • In addition to the methods described for the treatment of NF1, there are other treatment options for NF2 • For NF2, and MRI will show the appearance of the tumor and surgery is an option to remove tumors and correct cataracts and retinal abnormalities • So early recognition is paramount in prevention

18. TreatmentSchwannomatosis • There is no treatment currently available for Schwannomatosis but surgery is the best option • Genetic testing is also available for families with histories of NF1 and NF2, but currently there is no testing for Schwannomatosis

19. Current Research • The position of the gene that predisposes an individual for NF1 is located on chromosome 17 • the associated protein is called neurofibromin and is primarily located in nerve cells • it is part of the regulation of cell division in neurons • Neurofibromin is a tumor suppressor gene whose function is to inhibit the p21 rasoncoprotein, so if mutated, tumors will not be suppressed, which is problematic

20. Current Research • The NF2 gene is located in chromosome 22 and the product is a protein that is a tumor suppressant protein called merlin or schwannonim • Merlin apparently regulates growth in specific cells, Schwann cells and meningeal cells

21. Current Research • When researchers can figure out the exact 3D shape, something can be done in the production of a drug or through an application of gene therapy to remove, or repair the gene entirely • Schwannomatosis is a product of a mutation on chromosome 22 and 17 • Researchers are also trying to determine more about what the protein Merlin controls within the cell

22. Current Research • In addition to the Merlin protein, researchers are trying to determine more about the protein neurofibromin and its association to other genes and disabilities • If a child does not have abnormal skin spots, the goal in treatment is to prevent the development of neurofibromas, or tumors

23. Current Research • With regards to cancer research in preventing tumors from developing and growing, more efforts are being put into three categories • Cytotoxics (cell poisons) • Antihormonals (block hormone receptors) • Adjuvants (drugs which supplement the performance of the main drug)

24. Current Research • As the Ras pathway is very intimately associated with NF, a lot of research is being put in to inhibit the biochemical pathway • It is also important to figure out which Ras protein pathway is affected by NF

26. Works Cited • "Defining the Future of Neurofibromatosis Research." National Institute of Neurological Disorders and Stroke (NINDS). Web. 28 Feb. 2011. <http://www.ninds.nih.gov/news_and_events/proceedings/neurofibromatosis_wkshp.htm>. • "Neurofibromatosis Information Page." National Institute of Neurological Disorders and Stroke (NINDS). Web. 28 Feb. 2011. <http://www.ninds.nih.gov/disorders/neurofibromatosis/neurofibromatosis.htm>. • "Neurofibromatosis." Wikipedia, the Free Encyclopedia. Web. 28 Feb. 2011. <http://en.wikipedia.org/wiki/Neurofibromatosis>. • "Schwann Cell." Wikipedia, the Free Encyclopedia. Web. 28 Feb. 2011. <http://en.wikipedia.org/wiki/Schwann_cell>. • "Schwannomatosis | Learn About NF." The Children's Tumor Foundation - Neurofibromatosis, NF, NF1, NF2, Schwannomatosis. Web. 28 Feb. 2011. <http://www.ctf.org/Living-with-NF/schwannomatosis.html>. • "Solubility Product Constants." Kemijsko-tehnološki Fakultet U Splitu. Web. 26 Feb. 2011. <http://www.ktf-split.hr/periodni/en/abc/kpt.html>.

27. Works Cited • British Columbia Neurofibromatosis Foundation. Web. 27 Feb. 2011. <http://www.bcnf.bc.ca/learn-more/nf-1/>. • Chambers, :. Diana. "Neurofibromatosis-1: Treatment | Health32.Com." Health32.Com | General Health Information Online. Web. 28 Feb. 2011. <http://www.health32.com/neurofibromatosis-1-treatment-2/>. • "Neurofibromatosis Type 1." Learn.Genetics™. Web. 28 Feb. 2011. <http://learn.genetics.utah.edu/content/disorders/whataregd/nf1/>. • "Figure 3 : Neurofibromatosis Type 1 [mdash] a Model for Nervous System Tumour Formation? : Nature Reviews Cancer." Nature Publishing Group : Science Journals, Jobs, and Information. Web. 28 Feb. 2011. <http://www.nature.com/nrc/journal/v5/n7/fig_tab/nrc1653_F3.html>. • British Columbia Neurofibromatosis Foundation. Web. 27 Feb. 2011. <http://www.bcnf.bc.ca/learn-more/nf-1/>. • "KICK Neurofibromatosis Print from Zazzle.com." Zazzle | Custom T-Shirts, Personalized Gifts, Posters, Art, and More. Web. 28 Feb. 2011. <http://www.zazzle.com/kick_neurofibromatosis_poster-228922366357868822>.