By Jared Lauterbach and Josh Dardick

Neurofibromatosis (NF)

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.

What is NF?

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

What causes NF

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.

What Causes NF?

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.

Likelihood of getting it?

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.

Likelihood?

How it works in its simplest form…

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.

NF 1?

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

Diagnosis of NF 1

Café-au-lait spot on patient’s cheek

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.

NF 2?

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.

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.

Schwannomatosis?

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.

Clarify!

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.

Life Expectancy

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.

Treatments/Cure?

Before

Removal Surgery

After

http://www.ctf.org/Living-with-NF/learn-about-nf.html http://www.mayoclinic.org/neurofibromatosis/ http://nfcure.org/nfcureproject/

nfcureprojecthistory.html

Bibligraphy