1. 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 – /S (14)
Pong W, Gutmann D. The ecology of brain tumors: lessons learned from neurofibromatosis- 1. Oncogene [serial online]. March 10, 2011;30(10): 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.