Neurofibromatosis

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at May 30, 2016
StartDiseasesNeurofibromatosis

Neurofibromatosis is a genetic disorder of the central nervous system. It refers to three unique conditions, which can be inherited or occur as a result of a spontaneous genetic mutation. These conditions cause the formation of tumors along nervous tissue.

Contents

Definition & Facts

Roughly 100,000 people in the United States have one of the neurofibromatosis disorders. Neurofibromatosis 1 (NF1) is the most common type of neurofibromatosis, and it causes neurofibromas, which are benign fleshy growths that occur along the top and interior of the skin.

Neurofibromatosis 2 (NF2) is a less common form of neurofibromatosis that is characterized by benign tumors on the cranial nerves and spinal nerves, particularly along the nerves that carry sound from the ears to the brain. Schwannomatosis is a very rare type of neurofibromatosis that was originally thought to be a version of NF2; people with schwannomatosis get painful yet noncancerous tumors on both spinal and peripheral nerves

Symptoms & Complaints

The symptoms associated with NF1 typically become evident between birth and the age of 10. There are many physical symptoms of NF1, including having over six café au lait spots, which are light brown, flat areas of pigment on the skin, freckles near the armpits and groin, large heads, short stature, deformed spine and leg bones, and small bumps on the iris of either eye.

The characteristic neurofibromas of NF1 are mostly in or below the skin, but they can also develop on internal nerves. Mild learning disabilities, such as ADHD, are also common among children with NF1.

The tumors and other symptoms of NF2 grow at a much slower rate, so this condition typically is not diagnosed until early adulthood. The primary symptom of NF2 is tumors growing on the auditory nerves, which causes slow hearing loss, ringing ears, difficulty balancing, and headaches.

The tumors of NF2 can also grow on the optic nerves or other nerves, causing vision problems, numb limbs, and drooping facial features. Schwannomatosis symptoms are similar to NF2, but tumors do not typically grow on auditory nerves, and people suffering from schwannomatosis also experience widespread chronic pain.

Causes

All types of neurofibromatosis disorders are caused by a genetic mutation. About half of all people with neurofibromatosis 1 or 2 inherit this mutation from a parent, while the other half have a spontaneous mutation that has no known cause. The heritable genetic mutations that can cause neurofibromatosis are dominant. This means that even if just one parent has the condition, the parents' children can still inherit the condition.

A person with neurofibromatosis has a 50 percent chance of passing it on to any offspring. However, severity of neurofibromatosis disorders is not inherited, so a parent with severe NF1 may have a child who has mild NF1.

NF1 is caused by a mutated gene in chromosome 17, and this mutated gene prevents the body from producing neurofibromin, a protein that prevents cells from growing unchecked. NF2 is caused by a mutated gene in chromosome 22, and this mutation prevents the growth of a protein called merlin, which is a tumor suppressor gene, and this mutation also causes uncontrolled cellular growth.

Only 15 percent of people with schwannomatosis inherit it from a parent, and the other cause of this rare condition is an unknown genetic mutation. Medical researchers know that genetic mutations of the SMARCB1 gene cause schwannomatosis, but they are not aware of the precise reason why these mutations occur.

Diagnosis & Tests

Since neurofibromatosis is often inherited from a parent, a review of family history and medical history is typically the first step in a diagnosis. A physical examination can also reveal many of the telltale tumors or café au lait spots associated with NF1. If a child has at least one sign of NF1, the doctor will most likely recommend further monitoring to see if more symptoms develop. To diagnose NF1, it is necessary for a patient to have at least two symptoms of the condition.

If a family medical history and a physical exam do not show enough signs of a diagnosis, more tests can be done. Eye examinations and ear examinations can be used to diagnose any vision and hearing difficulties. X-rays will be able to show any of the bone deformities associated with NF1. To see the interior tumors caused by all types of neurofibromatosis, MRIs and CT scan may be employed.

To further confirm the neurofibromatosis diagnosis, genetic tests can be done to look for the genetic mutations associated with the disease. These genetic tests can even be done prenatally to diagnose neurofibromatosis in a fetus. However, genetic tests for schwannomatosis are not always precise, since the exact genetic causes are still unknown.

Treatment & Therapy

There is no way to fix the genetic mutations that cause neurofibromatosis disorders, but there are several ways to manage symptoms of the condition. Tumors can be removed with surgery or precision radiation, and when these tumors are removed, hearing loss or nerve pain can be alleviated.

For people who already have nerve damage from tumors, cochlear implants can help to further treat hearing loss. For people with nerve pain, doctors may prescribe gabapentin, pregabalin, serotonin, topiramate, or amitriptyline to ease the widespread pain.

Doctors emphasize that constant monitoring of symptoms is necessary to manage neurofibromatosis disorders. With constant monitoring, tumors can be removed before they grow large enough to damage nerves, cause pain, or cause hearing and vision loss. Though it is rare for neurofibromatosis tumors to become cancerous, monitoring symptoms will often reveal cancerous tumors at an early enough stage for easy treatment.

Prevention & Prophylaxis

There is no known way of preventing the gene mutations that can spontaneously cause neurofibromatosis. Prenatal genetic screening may be opted for by some prospective parents.

Though there is no way to prevent neurofibromatosis, it is possible to prevent some of the worse symptoms from developing with frequent checkups and proper treatment.