Neurofibromatosis is an incurable genetic disorder of the nervous system. It mainly affects the development of nerve cell tissues. Tumors known as neurofibromas develop on the nerves, and these can lead to other problems.
The tumors may be harmless, or they may compress the nerves and other tissues, leading to serious damage.
Neurofibromatosis (Nf) is the most common genetic neurological disorder that is caused by a single gene. The mutation in the gene means that the nerve tissue is not properly controlled.
There are three types: Nf1, Nf2, and schwannomatosis. They are not related. This article will focus mainly on Nf1 and Nf2.
Although there is no cure for neurofibromatosis, its symptoms can be treated.
Neurofibromas are not generally painful, but if their location on the body means that they graze or catch on clothing, they can be removed. This reduces the risk of itching, infection, numbness, and general discomfort. However, they may grow back.
Hypertension can be treated with medications and lifestyle changes. Regular checks are advised.
If tumors growing on the optic nerve are affecting eyesight, they can be surgically removed.
Scoliosis, or curvature of the spine, can be corrected through surgery or by wearing a back brace.
Normally, the tumors are regularly monitored, and treatment is given as required.
Surgery for acoustic neuromas does not always improve hearing and may worsen it. The decision to remove an acoustic neuroma will depend on the size of the tumor and how rapidly it is growing, not only on hearing loss.
Sometimes a surgeon will insert an auditory brain stem implant (ABI) to help a person’s hearing. They may remove a vestibulocochlear nerve tumor at the same time.
The surgeon will make an incision in the skin of the side of the head and remove some of the bone behind the ear. This exposes the tumor for removal and gives access to the brain stem below.
People with an ABI wear an external receiver and speech processor. This converts sound into electrical signals, which are then sent to the implant.
A cochlear implant may be fitted after removing the tumor. This small, complex electronic device can help to provide a sense of sound for someone with profound or severe hearing problems.
An external portion is placed behind the ear, and a second portion is surgically placed under the skin. The implant consists of a microphone, a speech processor, and a transmitter and receiver or stimulator, to receive signals from the speech processor and convert them into electric impulses.
A group of electrodes collects the stimulator impulses and sends them to different parts of the auditory nerve.
The implant cannot restore normal hearing, but it can provide a useful representation of sounds, and this can help a person to understand speech.
An audiologist can advise on managing balance and tinnitus, or ringing in the ears. Some people with neurofibromatosis learn to lip read and use sign language.
Radiotherapy or chemotherapy may help to shrink a tumor, and work is under way to find a drug that could prevent or reduce the tumors.
The symptoms of neurofibromatosis depend on the type.
The disorder can spread throughout the whole body, leading to tumors and unusual skin pigmentation.
It can manifest as bumps under the skin, colored spots, bone problems, pressure on spinal nerve roots, and other neurological problems.
Learning disabilities, behavioral problems, and vision or hearing loss may arise.
Some individuals with Nf1 have only a skin condition and no other related medical problems. Signs and symptoms generally appear during early childhood. They are not usually harmful to health.
Birthmarks and freckles are common. Coffee-colored marks appear on the skin, usually at birth. If more than six marks appear by the age of 5 years, this may indicate Nf1. The number of spots can increase, and they may grow larger and darker with time.
Freckles may appear in an unusual location, such as the groin, under the breasts, or in the armpits.
Neurofibromas are tumors, generally non-cancerous, that grow on the nerves of the skin, and sometimes on nerves deeper inside the body. They look like lumps under the skin. In time, more may develop, and they may get bigger. Neurofibromas may be soft, or firm and round.
Lisch nodules can also occur. These are very small brown spots that may appear in the iris of the eye.
People with Nf1 also face a higher risk of hypertension, or high blood pressure.
Nf2 is a more serious condition in which tumors grow on nerves deep inside the body.
An acoustic neuroma is a common type of brain tumor that develops on the nerve that goes from the brain to the inner ear.
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 may get worse as the tumor grows. The neuroma may compress the brainstem, which can be life-threatening. A small tumor may not cause any problems.
Sometimes, tumors develop on the skin, brain, and spinal cord, with potentially serious consequences. Some tumors develop rapidly, but most grow slowly, and the effect may not be noticeable for several years.
Regular monitoring can enable tumors to be removed before complications arise.
Spots of light brown pigmentation may occur, but they will be less common and fewer in number than in people with Nf1.
Cataracts may occur. If a child develops a cataract, this may be a sign of Nf2. These are easily removed, and not generally problematic if treated.
The three types of neurofibromatosis are Nf1, Nf2, and schwannomatosis.
Type 1 neurofibromatosis (Nf1)
Also known as von Recklinghausen’s disease, von Recklinghausen NF, or peripheral neurofibromatosis, NF1 is the most common type of neurofibromatosis. It mostly results from a mutation, rather than a deletion, of the Nf1 gene. It is thought to affect 1 in every 3,000 people.
Shortly after birth, birthmarks may appear in different parts of the body.
During late childhood, lesions, or tumors, may appear on or under the skin, numbering from a few to thousands. Occasionally, the tumors become cancerous.
Nf1 can be barely noticeable, it can be unsightly, or it can lead to potentially serious complications. Around 60 percent of cases are minor.
Did the ‘elephant man’ have Nf1?
It is a common misconception that Joseph Merrick, the “Elephant Man,” made famous by the 1980 movie starring John Hurt, had Nf1.
However, in 1986, geneticists showed that Merrick had not Nf1 but Proteus syndrome, a rare condition that affects fewer than 1 in 1 million people.
Researchers say that confusing the two conditions may be harmful to people with Nf1.
In a study published in 2011, Claire-Marie Legendre and co-authors point out:
“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 neurofibromatosis, or Nf2, normally stems from a mutation, rather than a deletion, of the Nf2 gene. It is transmitted on a different chromosome to Nf1.
Tumors form in the nervous system, generally within the skull. These are known as intracranial tumors. Intraspinal tumors may develop in the spinal canal.
Acoustic neuromas are common in Nf2, forming on the vestibulocochlear nerve, or the eighth cranial nerve.
The vestibulocochlear nerve is responsible for hearing and affects a person’s sense of balance and body position, so a loss of hearing and balance may occur.
Symptoms tend to arise during the late teens and early twenties. Tumors may become cancerous.
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.
Neurofibromatosis can affect all neural crest cells, including Schwann cells, melanocytes, and endoneurial fibroblasts. It may affect the bones, causing severe pain.
A mutation of a gene also known as Nf1 causes Nf1. This gene normally produces a protein that keeps the growth of nerve tissue in check.
However, in people with the condition, the gene produces an incomplete protein. This protein is far less effective at moderating the growth of tissue in the nervous system, and this leads to the tumors that develop in someone with Nf1.
This gene is located on chromosome number 17.
Nf2 affects a similar gene on chromosome number 22.
Both major types are passed from a parent to a child in roughly half of all known cases, and only one parent needs to have the faulty gene for a child to face a risk of developing neurofibromatosis.
In the other half of cases, these genes will undergo what is known as a sporadic mutation in a sperm or egg cell. The causes and risk factors of sporadic mutations are unclear.
In Nf2, the mutation can also occur after the conception of an embryo in a form called Mosaic Nf2. This is a milder form of the disease.
Nf1 is normally diagnosed during childhood. A diagnosis is confirmed when an individual has at least two of the following:
- 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 around 25 percent of people with Nf1. Plexiforms are neurofibromas that spread around large nerves as they grow, causing the nerve to become thick and misshapen. They feel like knots or cords under the skin. They can be large, painful, and disfiguring. Plexiforms normally start to form during childhood.
A special lamp is used to check for skin marks. Other diagnostic tools include an X-ray, CT, or MRI scan. A genetic blood test may also be used.
Symptoms of Nf2 normally appear around puberty or in adulthood. The most common age of onset tends to be from 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 person with Nf2 will be referred to a neurologist. Hearing and eye tests can check for cataracts, other eye problems, and hearing problems.
The complications for each type of neurofibromatosis are different.
Complications of Nf1
Vision and hearing problems can occur if a tumor, or neuroma, presses on the nerves leading to the ears or eyes. Children may experience learning and behavioral challenges as a result.
Around 50 percent of children with Nf1 face learning challenges. Short-term memory, spatial awareness, and coordination may also be affected.
Other complications of Nf1 include:
- 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
- problems with speech
- short stature
- skeletal problems
There may be early or late sexual development and puberty.
Complications of Nf2
People with Nf2 can develop benign skin tumors, similar to those characteristic of NF1. These should be monitored in case they grow, change, or cause pain.
Benign brain tumors may put pressure on parts of the brain and cause convulsions, eyesight problems, and balance problems. Some become cancerous.
Spinal cord tumors may develop on the nerves surrounding the spine, resulting in trembling, numbness, and pain in the limbs. Tumors around the neck area may cause facial problems, for example, difficulty with smiling, blinking, or swallowing.
Many people with Nf1 have only mild symptoms and can live a normal, healthy life. Complications may shorten the lifespan, but a person with Nf1 can often expect to live for the same amount of time as someone without the condition.
However, symptoms will need regular monitoring to prevent complications from developing.
Nf2 has a less positive outlook. Although its tumors are generally benign, the location and quantity of tumors can impair quality of life and cause early mortality. On average, people with Nf2 live to the age of 36 years.