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.
Nf1 and Nf2 are caused by a genetic mutation. The mutation is often inherited, but between 30 and 50 percent result from an altered gene, which most likely happened spontaneously in the egg or sperm just before fertilization.
If a person has the altered gene, it can be passed on to future generations. If one parent carries a faulty gene, any offspring have a 50 percent chance of inheriting it.
This article will focus mainly on Nf1 and Nf2.
Contents of this article:
How does neurofibromatosis affect the body?
Birthmarks and freckles are a common sign of Nf1.
Neurofibromatosis can affect all neural crest cells, including Schwann cells, melanocytes, and endoneurial fibroblasts. It may affect the bones, causing severe pain.
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.
Types of neurofibromatosis
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 is transmitted on chromosome 17. 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 has been 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 for 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 chromosome 22.
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, forming on the vestibulocochlear nerve, or the eighth cranial nerve.
The vestibulocochlear nerve is responsible for hearing, and it affects the 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 20s. Tumors may become cancerous.
Schwannomatosis is a rare form of neurofibromatosis, genetically distinct 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, the nerve that goes to the ear. It does not involve the neurofibromas characteristic of Nf1 and Nf2.
The tumors can cause severe pain, numbness, tingling, and weakness in the toes and fingers.
Signs and symptoms
The signs and symptoms of neurofibromatosis depend on the type.
Some patients 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.
Skin growths may occur with both Nf1 and Nf2.
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, they may get bigger, and they may darken 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 are very small brown spots that may appear in the iris of the eye.
Nf2 is a more serious condition in which tumors grow on nerves deep inside the body.
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 worsen 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 less common and fewer in number than in patients 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.
Diagnosis, treatment, and complications
Nf1 is normally diagnosed during childhood. A diagnosis is confirmed when a patient has at least two of the following:
- 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, and a genetic blood test.
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 will check for cataracts, other eye problems, and hearing problems.
Treatment and complications
Many patients with Nf1 have only mild symptoms and can live a normal healthy life. However, they will need monitoring to prevent complications from developing.
Although there is no cure for neurofibromatosis, symptoms can be treated.
Neurofibromas are not generally painful, but if the location on the body means that they graze or catch on clothing, they can be removed. This reduce 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 affect the patient's 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 monitored regularly, and treatment given as required.
Surgery for acoustic neuromas does not always improve hearing, and it may worsen it. The decision to remove it will depend on the size of the tumor and how rapidly it is growing, not only on hearing loss.
A cochlear implant can help people with hearing loss.
Sometimes a surgeon will insert an auditory brain stem implant (ABI) to help 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 removes 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 sounds into electrical signals, which are then sent to the implant.
A cochlear implant may be placed 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 patients learn to lip read and use sign language.
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 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 get bigger, 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.