Neurofibromatosis Eldar Kurtovic School of Engineering University of Bridgeport, CT OBJECTIVE CHARACTERISTICS AND PROGRESSION The primary objectives of this poster is the following: Definition and Fundamentals Characteristics and Progression Screening and Diagnosis References Genetic characteristics NF1- Nonsense, Missense, Frameshift, Single and multiple exon deletions are common High/Low grade Gliomas, Astrocytomas, MPNSTs (malignant peripheral nerve sheath tumours ), Neuroblastomas NF2- Nonsense, Frameshift, Encodes Merlin (protein) that structural cytoskeleton-membrane linker, localizes to areas of membrane remodeling, linker btw/ plasma membrane + actin cytoskeleton, inhibits the Ras pathway at cell-ECM junctions, tumor suppressor. DEFINITION AND FUNDAMENTALS Structural changes in gene mutation, rapid proliferation of malignant tumors across the body, skin discoloration, tumor growths around nerve cells, and low concentrations of Vitamin D [1] 2 Types : NF1 and NF2 NF1 individuals dominantly“ develop neurofibromas, and Malignant Peripheral Nerve Sheath Tumors (MPNST) NF2 patients develop schwannomas and meningiomas [2]. NF2 is ”dominantly inherited tumor predisposition syndrome caused by mutations in the NF2 gene on chromosome 22” [3]. MITOSIS AND MEIOSIS Figure 1 Process of Meiosis Meiotic Cell division reduces chromosome number In both Mitosis and Meiosis, chromosomes line up during metaphase Chromosomes are distributed equally in both during first 2 nuclear divisions Final product is 4 daughter haploid cells Figure 1 Potential cellular interactions in the plexiform neurofibroma microenvironment. NGF indicates nerve growth factor; and MMP, matrix metalloproteinase. (Helfferich J et al. 2016) CLINICAL SCREENING ADVANTAGES/DISADVANTAGES Advantage: simple, effective not harmful time efficient Disadvantage: NF1 signs may show up as child progresses into adulthood delayed diagnosis, patient may have mild signs REFERENCES Genetic Testing: Advantage: early diagnosis (pre-sympthoms) if mutation exists- test other family members test can be done on pregnancy Disadvantage: prediction of severity is limited negative result doesn’t mean you don’t have it/ won’t get it time consuming REFERENCES Hirbe, Angela & David H Gutmann, Dr. (2014). Neurofibromatosis type 1: A multidisciplinary approach to care. The Lancet Neurology. 13. 834–843. 10.1016/S1474 4422(14)70063-8. Pong W, Gutmann D. The ecology of brain tumors: lessons learned from neurofibromatosis- 1. Oncogene [serial online]. March 10, 2011;30(10):1135-1146. Available from: Academic Search Premier, Ipswich, MA. Accessed October 2, 2017. [Nguyen R, Kluwe L, Fuensterer C, Kentsch M, Friedrich RE, Mautner VF. Plexiform neurofi bromas in children with neurofi bromatosis type 1: frequency and associated clinical defi cits. J Pediatr 2011; 159: 652–55.e2.