What’s to know about neurofibromatosis?

Neurofibromatosis is an incurable nervous-system genetic disorder. It mainly impacts nerve cell tissue growth. Tumors known on the nerves as neurofibromas develop, and these may lead to other problems.

The tumors may be harmless, or may compress nerves and other tissues, resulting in severe damage.

Neurofibromatosis (Nf) is the most common neurological genetic condition caused by a single gene. The gene mutation means the nerve tissue isn’t properly controlled.

Three forms exist: nf1, nf2, and schwannomatosis. They are not linked to each other. This article focuses primarily on Nf1 and Nf2.

Treatment

 A lady under cochlear implant
A cochlear implant can help people with hearing loss.

While neurofibromatosis has no cure, its symptoms can be treated.

Neurofibromas are not normally harmful but they may be removed if their position on the body means they graze or catch on clothes. This reduces the chance of scratching, infection, numbness and pain in general. They can however grow back.

Medications and lifestyle improvements can be used to treat Hypertension. Daily inspections are recommended.

If eyesight is compromised by tumors arising on the optic nerve, these may be removed surgically.

Scoliosis, or spine curvature, may be treated by surgery, or by wearing a back brace.

Tumors are typically monitored periodically, and care is administered as appropriate.

Acoustic neuroma

Acoustic neuromas surgery does not always enhance hearing, and can make it worse. The decision to remove an acoustic neuroma will depend on the tumor size and how rapidly it develops, not just hearing loss.

Often, an auditory brain stem implant (ABI) is implanted by a surgeon to help a person hear. We can at the same time remove a tumor in the vestibulocochlear nerve.

The surgeon must make an incision on the side of the head in the skin and remove some of the bone from behind the ear. This reveals the tumor and provides access to the brain stem below for removal.

Individuals with an ABI wear external receivers and speech processors. It transforms sound into electrical signals which will be sent to the implant afterwards.

After the tumor has been removed a cochlear implant can be mounted. A tiny, complex electronic system will help give someone with serious or extreme hearing issues a sense of sound.

An outer portion is placed behind the ear, and a second portion under the skin is surgically inserted. The implant consists of a amplifier, a speech processor, and a transmitter and receiver or stimulator to absorb signals and transform them into electrical impulses from the speech processor.

The stimulator impulses are received by a group of electrodes and sent to various parts of the auditory nerve.

The implant is unable to restore natural hearing, but it does provide useful sound reproduction and this can help a person understand speech.

An audiologist can advise on managing tinnitus and balance, or ringing in the ears. Some people suffering from neurofibromatosis learn to read lips and use sign language.

Radiotherapy or chemotherapy can help shrink a tumor, and research is ongoing to find a drug that can eliminate or reduce tumors.

Symptoms

The neurofibromatosis symptoms are dependent on the type.

The disorder can spread all over the body, leading to tumors and irregular pigmentation of the skin.

It can manifest as bumps under the skin, dark spots, bone problems, pressure on the roots of the spinal nerve and other neurological issues.

You may experience learning disorders, behavioral problems, and loss of vision or hearing.

Nf1

Some people with Nf1 have only one skin disorder, and no other associated medical issues. In general, signs and symptoms occur during early childhood. They seem not to be harmful to health.

Skin growths may occur with both Nf1 and Nf2.
Skin growths may occur with both Nf1 and Nf2.

Birthmarks are common, and so are the freckles. Coffee-colored marks typically develop on the skin at birth. Where more than six marks appear at 5 years of age, this may mean Nf1. The number of spots may increase, and over time they can get bigger and darker.

Freckles can occur under the breasts or in the axes at an unusual position, such as the groin.

Neurofibromas are tumors, normally non-cancerous, which develop on the skin’s nerves, and often on deeper within the body’s nerves. Under the the skin they feel like lumps. They may grow over time, and they can get bigger. Neurofibromas may be soft, or round and firm.

Lisch nodules can also be present. There are very small brown spots that can appear in the eye iris.

People with Nf1 often face a higher risk of high blood pressure, or hypertension.

Nf2

Nf2 is a more serious condition where tumors develop deep within the body on nerves.

An acoustic neuroma is a common type of brain tumor that spreads from the brain to the inner ear into the nerve.

Symptoms may include:

  • facial numbness, weakness and sometimes paralysis
  • gradual, or more rarely sudden, hearing loss
  • loss of balance, dizziness, and vertigo
  • tinnitus, or ringing in the affected ear

Symptoms can worsen as the tumor grows. The neuroma can compress the brainstem, which is potentially life-threatening. There could be no complications with a small tumor.

Tumors develop sometimes on the skin, brain, and spinal cord, with potentially severe consequences. Some tumors develop rapidly, but most grow slowly, and for several years the effect may not be noticable.

Regular monitoring can allow for the removal of tumors before complications occur.

Light brown pigmentation spots can occur but they will be less common and less numerous than in Nf1 people.

Cataracts can happen. That could be a symptom of Nf2 if a child develops a cataract. These are easily removed, and are not usually troublesome when treated.

Types

The three types of neurofibromatosis are Nf1, Nf2, and schwannomatosis.

Type 1 neurofibromatosis (Nf1)

The most common type of neurofibromatosis is NF1, also known as von Recklinghausen’s disease, von Recklinghausen NF, or peripheral neurofibromatosis. This results more from a mutation of the Nf1 gene, rather than a deletion. 1 in every 3000 people is thought to be affected.

Birthmarks can show up in different parts of the body shortly after birth.

Late childhood lesions, or tumors, can appear on or below the skin, counting from a few to thousands. The tumors also become cancerous.

Nf1 can hardly be seen, it can be unsightly or it can lead to problems that are potentially dangerous. Of the cases, about 60 percent are minor.

Did the ‘elephant man’ have Nf1?

It’s a common misconception that Nf1 was made famous by Joseph Merrick, the “Elephant Man,” the 1980 movie starring John Hurt.

In 1986, however, geneticists revealed that Merrick did not have Nf1 but Proteus syndrome, a rare disorder affecting less than 1 in 1 million people.

Researchers suggest uncertainty between the two conditions may be detrimental to people with Nf1.

Claire-Marie Legendre and co-authors point out in a study published in 2011:

“Confusing NF1 with the Elephant Man’s condition harms the interests of those with NF1, all the more so because it is known that NF1 sufferers experience difficulty establishing social ties and developing good self-esteem.”

The authors call for changes in attitude to dispel the confusion.

Type 2 neurofibromatosis (Nf2)

Bilateral neurofibromatoses, or Nf2, are usually caused by a mutation of the Nf2 gene, rather than a deletion. It is transmitted into Nf1 on a separate chromosome.

In the nervous system, tumors form, usually inside the skull. These are called intracranial tumors. Tumors in the intraspinal spinal canal may develop.

Acoustic neuromas that develop on the vestibulocochlear nerve, or the eighth cranial nerve, are typical in Nf2.

The vestibulocochlear nerve is responsible for hearing and affects the sense of balance and position of a person’s body so that a hearing and balance loss may occur.

Symptoms tend to arise during the late teens and early twenties. Tumors may become cancerous.

Schwannomatosis

Schwannomatosis is a rare form of neurofibromatosis that is genetically different from Nf1 and Nf2. It affects fewer than 1 in 40,000 people.

Schwannomas, or tumors in the tissue around a nerve, can develop anywhere in the body, except for the vestibulocochlear nerve, which is the nerve that goes to the ear. It does not involve the neurofibromas that are common in Nf1 and Nf2.

The tumors can cause severe pain, numbness, tingling, and weakness in the toes and fingers.

Causes

Birthmarks and freckles are a common sign of Nf1.
Birthmarks and freckles are a common sign of Nf1.

Neurofibromatosis can affect all cells of the neural crest, including those of Schwann, melanocytes, and endoneurial fibroblasts. It can damage the bones and cause intense pain.

Nf1 causes a gene mutation also known as Nf1. This gene normally yields a protein that keeps nerve tissue growth in check.

However the gene produces an incomplete protein in people with the disease. This protein is much less effective in moderating tissue growth in the nervous system, and this leads to tumors developing in someone with Nf1.

This gene is found on the 17th chromosome.

On chromosome number 22 Nf2 affects a related gene.

In roughly half of all known cases, both major types are passed from a parent to a child, and only one parent needs the faulty gene for a child to face the risk of developing neurofibromatosis.

In the other half of cases, those genes in a sperm or egg cell will undergo what is known as a sporadic mutation. The causes of sporadic mutations and their risk factors are unclear.

The mutation may also occur in Nf2, after an embryo is conceived in a form called Mosaic Nf2. This is a milder type of the illness.

Diagnosis

Nf1 is normally diagnosed in infancy. A diagnosis is confirmed when a person has at least two of these:

  • a family history of Nf1
  • a glioma, or tumor, on the optic nerve, usually without symptoms
  • lesions in the bone
  • at least six “café-au-lait” spots measuring more than 5 millimeters across in children or 15 millimeters in adolescents and adults
  • at least two Lisch nodules, or small brown spots in the iris
  • freckling in the armpits, under the breast, or in the groin area
  • two or more neurofibromas, or one “plexiform”

Plexiforms affect approximately 25 percent of Nf1 men. Plexiforms are neurofibromas that spread as they expand around large nerves, causing the nerve to become thick and disfigured. They sound like knots under the fat, or ropes. They may be tall, painful and disfiguring. Plexiforms usually begin to develop during infancy.

To test for marks on the skin a special lamp is used. Many methods for the diagnosis include an X-ray, CT or MRI scan. In addition, a genetic blood test may be used.

Diagnosing Nf2

Symptoms of Nf2 normally occur in adulthood or around puberty. The most prevalent starting age appears to be 18 to 24 years.

A diagnosis of Nf2 is made when there is:

  • acoustic neuroma in one ear, plus two or more typical symptoms, such as cataracts, brain tumors, and a family history of the condition
  • acoustic neuroma in both ears
  • acoustic neuroma plus brain or spinal tumors, detected by an MRI or CT scan
  • a faulty gene, identified through a blood test

A Neurologist will be assigned to a individual with Nf2. Hearing and eye testing will search for cataracts, other eye conditions and issues with hearing.

Complications

The complications for each type of neurofibromatosis are different.

Complications of Nf1

Problems of vision and hearing can occur when a tumor or neuroma presses on the nerves leading to the ears or eyes. As a result, children may suffer learning and behavioral challenges.

Approximately 50 percent of Nf1 children face learning challenges. It can also affect the short-term memory, spatial perception, and coordination.

Many Nf1 issues cover:

  • epilepsy
  • large head size
  • benign skin tumors that, in a few cases, may become cancerous
  • curvature of the spine, or scoliosis
  • gliomas, or tumors on the eye nerves, occasionally causing eyesight problems
  • hypertension
  • problems with speech
  • short stature
  • skeletal problems

There may be early or late sexual development and puberty.

Complications of Nf2

People with Nf2 may develop benign tumors in the skin, similar to the NF1 characteristics. These should be monitored if they are growing, changing or causing pain.

Benign brain tumors can place pressure on parts of the brain and cause seizures, problems with eyesight and problems with balance. Some get cancer.

Tumors of the spinal cord may develop on the nerves surrounding the spine, causing tremor, numbness and pain in the limbs. Tumors around the neck area can, for example , cause facial problems with smiling, blinking or swallowing.

Outlook

Many people with Nf1 have only mild symptoms, and they can live a healthy, normal life. Complications can shorten lifespan, but a person with Nf1 can still expect to live without the condition for the same period of time as anyone else.

Symptoms may need to be monitored periodically to prevent complications from forming.

There is a less optimistic view to Nf2. While its tumors are generally benign, the location and amount of tumors can impair quality of life and cause early mortality. People with Nf2 live on average until they are 36 years old.

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