Neurofibromatosis is a group of familial cancer syndromes that are characterized by the growth of multiple benign (non-cancerous) tumours on nerve tissue within the body. These tumours can develop anywhere in the body, but most commonly along the nerves in the brain, spinal cord, and skin.
The nervous system is made up of two primary components: the central nervous system (CNS), and the peripheral nervous system (PNS). The CNS is made up of the brain and spinal cord, and is responsible for all sensory and motor functions in the body. The PNS encompasses all nerves outside of the CNS, and is responsible for all involuntary functions in the body. The PNS is further subdivided into the autonomic nervous system (ANS) and the somatic nervous system (SNS). The ANS controls involuntary processes and glands, such as heart rate, blood pressure, respiration, and digestion. Comparatively, the SNS is responsible for voluntary and involuntary muscle movements, as well as transmitting sensory information to the CNS. A tumour along any of the nerves in the body can go unnoticed, or result in adverse health issues.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutattions in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
While neurofibromatosis is not classified as a cancer, it is equally severe and can be life-threatening. While the condition is generally associated with the development of benign tumours, in rare instances it can cause the development of malignant (cancerous) tumours.
Neurofibromatosis is generally diagnosed equally between the sexes. The average age of diagnosis often varies by subtype.
Types of Neurofibromatosis
There are three primary types of neurofibromatosis, which are classified by the type of tumour that develops and the location of the tumour.
Neurofibromatosis Type 1 (NF1)
Neurofibromatosis type 1 (NF1), also known as Von Recklinghausen’s disease, Von Recklinghausen neurofibromatosis or peripheral neurofibromatosis, is one of the most common inherited disorders that is generally diagnosed in childhood. It is caused by a mutation of a tumour-supressing gene (known as the NF1 gene) on chromosome 17, and is often associated with the development of some of the following tumours:
NF1 is often associated with changes of the skin and, in some cases, bone deformities.
Neurofibromatosis Type 2 (NF2)
Neurofibromatosis type 2 (NF2) is a less common disorder that generally develops between the ages of 18-24. It is caused by a genetic mutation of a different tumour suppressor gene (known as the NF2 gene) on chromosome 22, and is often associated with the development of some of the following tumours:
Unlike NF1, NF2 is not associated with the development of neurofibromas, and less commonly present with skin abnormalities.
Schwannomatosis
Schwannomatosis, also known as neurilemmomatosis, is a rare type of neurofibromatosis that generally develops between the ages of 30-60. This disorder is characterised by the development of multiple schwannomas, and in rare instances meningiomas, but does not meet the criteria for NF2. Schwannomatosis is caused by a mutation of either the SMARCB1 or LZTR1 genes, which are though to be tumour-suppressor genes on chromosome 22.
Schwannomatosis often develops along the nerves of the brain and spinal cord.
Treatment
When cancers are detected, they are staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, because neurofibromatosis is not a cancer, the disease is generally not staged or graded.
Your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
While there is no standard treatment plan for neurofibromatosis, the symptoms can often be managed using some of the following treatments:
- Observation.
- Surgery to remove as much of the tumour(s) as possible – often for symptomatic relief.
- Medications – often for pain relief.
- Clinical trials.
- Auditory brainstem implants and/or cochlear implants (for patients with NF2 who have hearing difficulties).
If you have developed a malignant tumour, chemotherapy, radiation therapy and/or palliative care may also be recommended.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
While the cause of neurofibromatosis remains unknown, some of the following factors may increase the likelihood of developing the disease:
- Having a family history of the disease.
- Genetic mutations on chromosomes 17 and/or 22, especially of the NF1, NF2, SMARCB1 or LZTR1 genes.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
The symptoms of neurofibromatosis often vary by subtype.
Symptoms of Neurofibromatosis Type 1
Symptoms of NF1 may include:
- Six or more café-au-lait spots (light brown skin patches, oval or irregularly shaped, often present at birth but can appear after).
- Two or more neurofibromas, which carry their own set of symptoms:
- Brown or pink nodules on the skin.
- Nodules with soft or firm consistency on the skin.
- Nodules that cause pain.
- Freckles in the underarm or groin areas.
- Two or more Lisch nodules (tiny tumours in the iris portion of the eye).
- Bone deformities, potentially including:
- Osseous (bony) lesions and malformations.
- Pseudoarthrosis (a false joint or unhealed fracture), often affecting the tibia bone in the lower leg.
- Sphenoid wing dysplasia (abnormal bone growth in the base of the skull).
- Scoliosis (abnormal spinal curvature).
- Kyphosis (severe abnormal spinal curvature).
- Short stature.
- Osteoporosis.
- Heart problems.
- The development of gliomas.
- Attention-deficit/hyperactivity disorder (ADHD).
- Macrocephaly (an enlarged head).
- Headaches.
- Glaucoma (progressive eye disease caused by damage to the optic nerve).
- Numbness and/or weakness in affected area(s).
- Pain in affected area(s).
- Seizures.
- Anxiety.
- Cognitive deficits and/or learning disabilities.
Symptoms of Neurofibromatosis Type 2
Symptoms of NF2 may include:
- Hearing loss, which may begin in early adolescence.
- Tinnitus (ringing in the ears).
- Difficulties with controlling facial expressions.
- Difficulties with balance.
- Difficulties with walking.
- Juvenile cataracts (a cloudy area in the lends of your eye that develops in juvenile/childhood years).
- Cranial nerve dysfunction, which carries its own set of symptoms:
- Intense pain in the head.
- Vertigo (dizziness).
- Weakness.
- Paralysis of affected area.
- Hydrocephalus (rare).
- Difficulties swallowing.
- Difficulties with eye movement.
- Numbness and/or tingling in affected areas.
- Muscle weakness in affected areas.
- Facial nerve palsy.
- Ocular proptosis (bulging of one or both eyes).
- Pain in affected area(s).
Symptoms of Schwannomatosis
Symptoms of schwannomatosis may include:
- The presence of two non-intradermal schwannomas or meningiomas.
- Numbness and/or tingling in affected area(s).
- Weakness in affected area(s).
- Changes in urinary and/or bowel habits.
- Facial weakness.
- Headaches.
- Lumps and/or swollen areas under the skin where tumours have forms.
- Vision changes.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have neurofibromatosis, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Genetic testing
In addition to guiding treatment, genetic testing can be used to help diagnose certain conditions. Neurofibromatosis has been linked to mutations in the NF1, NF2, SMARCB1 or LZTR1 genes, which all change specific protein functions. These changes can lead to cell abnormalities and, in extreme cases, cancer. Your doctor may perform genetic testing to better understand your condition.
Neurological examination
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength, and reflexes, depending on the signs and symptoms you have described. Any problem that is detected in this exam can help determine which portion of the CNS needs further investigation.
Imaging & Blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-rays, bone scan and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Electromyogram (EMG)
An electromyogram is a diagnostic procedure used to measure the response of nerves and skeletal muscles to electrical activity. For this test, small needles are inserted into your muscle and records the electrical activity in the muscle as you try to move it. This procedure is often performed by a specialist, and is often performed while you are awake.
Nerve Conduction Study
A nerve conduction study, also known as a nerve conduction velocity test, is a diagnostic procedure used to measure the speed of electrical impulses through a nerve. The test involves stimulating the nerves via small electrode patches on the skin with a very small electrical impulse. Nerve conduction studies are often performed alongside an EMG.
Biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. This tissue will then be sent to the lab and analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, neurofibromatosis has a good prognosis and survival rates. However, if the tumour has become malignant and/or has spread, the prognosis may not be as good, and there may be a higher risk of recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.