Transcript Neurofibromatosis (NF) - Boulder Valley School District

By Jared Lauterbach and Josh Dardick
 Neurofibromatosis (NF) is a disease in which tumors
can form on practically any part of the body. Also
called elephant man’s disease, NF affects many people
around the world.
 NF is caused by a genetic mutation to one of the 22
autosomal (non sex) chromosomes.
 It is a dominant trait. Being dominant means that only
one changed or affected gene causes the disorder to
appear.
 There are three types of NF: NF 1, NF 2, and
Schwannomatosis.
 NF 1 is caused by a mutation in a gene on chromosome




17.
The gene codes for a protein called neurofibromin.
This protein regulates the activity of another protein
called ras, which promotes cell division.
When the NF1 gene is mutated, it usually leads to a
shortened version of the neurofibromin protein that
cannot bind to ras or regulate its activity.
Cells are told to begin dividing and never told when to
stop, causing the formation of tumors
 NF 2 is caused by a mutation in Chromosome 22.
 Schwannomin is the cytoskeletal protein affected in
NF 2. It is a tumor suppressor protein.
 It is very similar to neurofibromin in that when it is
mutated, it allows for uncontrolled growth of tumors.
 The cause for Schwannomatosis is not fully
understood.
 There is a 50-50 chance of a child inheriting NF if one of




the parents have it.
If both parents were to have the gene then there would be a
greater chance of developing the disease.
If you draw a punnett square it is easy to see how it works
out.
If we use the letter N as the gene for NF and a lower case n
as the gene not affected by NF we see that there are three
genotypes. NN, Nn, nn.
There are two phenotypes in this case. The NN and Nn are
affected with NF since they carry the dominant trait.
 The nn genotype is not infected because it does not
have an N.
 These examples of genotypes may occur if the one or
two of the parents have the disease but research has
shown that half of all cases are not inherited but are a
result of a spontaneous mutation in the sperm or egg
cell.
 NF 1 occurring in 1: 3,000 births is characterized by Café-





au-lait spots (tan pigmented spots) on skin and
neurofibromas (benign nerve sheath tumor in the
peripheral nervous system) on or under the skin.
Neurofibromas typically begin to develop during puberty.
The presence of multiple neurofibromas is an important
diagnostic sign of NF.
The neurofibromas rarely become cancerous.
Enlargement and deformation of bones and curvature of
spin can occur. Tumors can also develop in brain and on
spinal cord.
Approximately 50% of people with NF 1 have learning
disabilities.
 Family history of NF1
 6 or more light brown ("cafe-au-lait") spots on the skin
 Presence of pea-sized bumps (neurofibromas) on the skin
 Larger areas on the skin that look swollen (plexiform




neurofibromas)
Freckling under the arms or in the groin area
Pigmented bumps on the eye's iris (Lisch nodules)
Skeletal abnormalities such as tibial dysplasia (bowing of
the legs), or thinning of the shin bone
Tumor on the optic nerve that may interfere with vision
 NF 2 occurring in 1:25,000 births is characterized by






multiple tumors on cranial and spinal nerves.
Other lesions of the brain and spinal cord can occur.
Hearing loss and problems with balance usually begins in
teens and twenties.
The tumors that occur in NF 2 patients are called
schwannomas because they arise from Schwann cells.
Schwann cells supported protect nerve cells and provide
nerve cells insulation.
Tumors that form on cranial nerves (gliomas) can push on
brain and affect the whole body.
Some tumors my form on spinal cord (meningiomas) and
can cause numbness in parts of the body.
 Another way to tell if you have NF 2 is if you have
multiple bilateral vestibular schwannomas (benign
tumor that develops from the balance and hearing
nerves supplying the inner ear).
 Symptoms such as hearing loss, vision loss, and
trouble with balance are important symptoms in the
diagnosis of NF 2.
 Schwannomatosis occurs in 1:40,000 births.
 Studies have shown that 85% of cases are found to be




sporadic and only 15% are inherited.
People with Schwannomatosis experience pain that can
occur in any part of the body.
Tumors can form on cranial, spinal and peripheral nerves.
People with this form of NF have multiple schwannomas
but do not develop vestibular tumors and do not go deaf.
They do not develop any other kinds of tumors that are
associated with NF 2. People with this form of NF do not
develop malignancies.
 Schwannomas and Neurofibromas have very important





similarities and differences.
They both originate in the insulating covering of peripheral
nerves.
Schwannomas are homogenous tumors consisting only of
nerve sheath cells or Schwann cells.
They stay on the outside of the nerve, but may push it aside
or against a bony structure causing damage.
Neurofibromas are heterogeneous tumors, which affect all
sorts of cells and structural elements in addition to the
Schwann cells.
They infiltrate the nerve and splay apart the individual
nerve fibers.
Woman with NF.
Some cases of NF can
be extreme such as
the case of this
woman. People with
NF can have trouble
being social because
of the physical
symptoms of their
disease. This is an
extreme case of NF.
 If there are no complications, the life expectancy of
people with NF is almost normal.
 It may be decreased by ten years or so if complications
arise.
 It is rare that the benign tumors associated with this
disease become cancerous so there are not a ton of
premature deaths.
 Victims of the disease can live a long life but may have
difficulties in normal life activities.
 There are no available treatments for





Neurofibromatosis.
To some extent the symptoms for NF can be treated
separately.
Tumors can be removed from skin, brain and spine.
Chemotherapy and radiation therapy can be used to
treat tumors.
Some tumors and Café-au-lait spots are removed if
they cause pain.
So far there are only treatments for the symptoms of
NF and no treatments are available for the cure of NF.
Before
After
 http://www.ctf.org/Living-with-NF/learn-about-nf.html
 http://www.mayoclinic.org/neurofibromatosis/
 http://nfcure.org/nfcureproject/nfcureprojecthistory.html