Neurofibromatosis is a group of genetic disorders that is characterized by the growth of multiple benignnot cancerous, can grow but will not spread to other body parts (non-cancerous) tumours on nerve tissuea group of cells that work together to perform a function within the body. These tumours can develop anywhere in the body, but most commonly along the nerves in the brain, spinal cord, and skin.
Familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations 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.
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, bloodthe red bodily fluid that transports oxygen and other nutrients around the body 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 tumoura tissue mass that forms from groups of unhealthy cells along any of the nerves in the body can go unnoticed, or result in adverse health issues.
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 malignantcancerous, may grow and spread to other areas of the body (cancerous) tumours.
Neurofibromatosis is generally diagnosed equally between the sexes. The average age of diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results 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 often associated with the development of some of the following tumours:
- Neurofibromas (most common).
- Optic nerve glioma.
- Malignant peripheral nerve sheath tumours (MPNSTs).
- Pheochromocytoma.
- Paraganglioma.
- Pancreatic NETs, potentially including:
- Wilms tumour.
- Rhabdomyosarcoma.
- Astrocytoma.
- Leiomyosarcoma.
- Ganglioglioma.
- Breast cancer.
- Juvenile myelomonocytic leukaemia (JMML).
- Gastrointestinal stromal tumours (GISTs).
- Colorectal cancer.
Neurofibromatosis Type 2 (NF2)
Neurofibromatosis type 2 (NF2) is a less common disorder that generally develops between the ages of 18-24. Unlike NF1, NF2 is not associated with the development of neurofibromas, less commonly present with skin abnormalities, and is often associated with the development of some of the following tumours:
- Schwannomas (most commonly vestibular schwannomas).
- Meningiomas.
- Ependymomas.
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 often develops along the nerves of the brain and spinal cord.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cellsthe basic structural and functional unit of all living things look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with neurofibromatosis will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignant (cancerous) or benign (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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:
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – often for symptomatic relief.
- Medications – often for pain relief.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Auditory brainstem implantsa device that is surgically inserted into the brain that provides sound to people who are deaf or hard of hearing and/or cochlear implantsa device that is surgically inserted into the inner ear that provides sound to people who are deaf or hard of hearing (for patients with NF2 who have hearing difficulties).
If you have developed a malignant tumour, the following may also be recommended:
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells (limited).
- Ablation therapya minimally invasive procedure that uses extremely high or low temperatures to destroy (ablate) abnormal tissue and/or cancer cells.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosis of neurofibromatosis has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. For patients with neurofibromatosis, the screening guidelines differ between subtypes.
Neurofibromatosis Type 1 Screening Guidelines
The screening guidelines for NF1 often differ between children and adults.
Childhood NF1 Screening Guidelines
For children with NF1, surveillance guidelines may include:
- Annual physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Annual eye exam until adolescence or as recommended by an ophthalmologist.
- Annual neurological exam, followed by an MRI if indicated by symptoms.
Adulthood NF1 Screening Guidelines
For adults with NF1, surveillance guidelines may include:
- Annual physical examination.
- Annual mammograma type of medical imaging that uses x-rays to create detailed images of breast tissue in females beginning at the age of 30.
- Annual breast MRI in females beginning around ages 30-50.
- Annual neurological exam, followed by an MRI if indicated by symptoms.
Neurofibromatosis Type 2 Screening Guidelines
The screening guidelines for NF2 may include:
- Annual physical examination.
- Annual neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination from infancy.
- Annual eye examination from infancy.
- Annual MRI of the brain and spinal cord between the ages of 10-20.
- MRI every three years after the age of 20, unless there are tumours present.
Schwannomatosis Screening Guidelines
Because of how rare schwannomatosis is, there hasn’t been any official screening recommendations made for this condition. Instead, your doctor will create a targeted screening program for you based on your individual circumstances.
Screening options for neurofibromatosis may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
Neurofibromatosis is a group of inherited autosomal disorders, which means that an affected parent has a 50% chance of passing the condition on to their children. It is caused by different genes, including:
- NF1 gene – a tumour suppressor gene on chromosome 17 (NF1).
- NF2 gene – a tumour suppressor gene on chromosome 22 (NF2)
- SMARCB1 gene – a tumour suppressor gene on chromosome 22 (Schwannomatosis).
- LZTRA1 gene – regulates cell growth and proliferation, found on chromosome 22 (Schwannomatosis).
Symptoms
The symptoms of neurofibromatosis often vary by the type(s) of tumours present. General symptoms of neurofibromatosis often vary by subtype.
General Symptoms of Neurofibromatosis Type 1
General symptoms of NF1 may include:
- Six or more café-au-lait spots (light brown skin patches, oval or irregularly shaped).
- 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 groinarea between the abdomen and thighs areas.
- Two or more Lisch nodules (tiny tumours in the iris portion of the eye).
- Bone deformities.
- Heart problems.
- Macrocephaly.
- 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.
General Symptoms of Neurofibromatosis Type 2
General symptoms of NF2 may include:
- Hearing loss, which may begin in early adolescence.
- Tinnitusringing in one or both ears (ringing in the ears).
- Difficulties with controlling facial expressions.
- Difficulties with balance.
- Difficulties with walking.
- Juvenile cataracts.
- Cranial nerve dysfunctionimpaired or abnormal function; not working properly, which carries its own set of symptoms:
- Intense pain in the head.
- Dizziness.
- Weakness.
- Paralysis of affected area.
- Hydrocephalusa build up of cerebrospinal fluid (CSF) in the brain, causing pressure and potentially damaging brain tissue (rare).
- Difficulties swallowing.
- Difficulties with eye movement.
- Numbness and/or tingling in affected areas.
- Muscle weakness in affected areas.
- Facial nerve palsy.
- Ocular proptosisbulging or protrusion of one or both of the eyes out of the eye sockets, also known as exophthalmos.
- Pain in affected area(s).
General Symptoms of Schwannomatosis
General 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 bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines habits.
- Facial weakness.
- Headaches.
- Lumps and/or swollen areas under the skin where tumours have forms.
- Vision changes.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with neurofibromatosis, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examination.
- Genetic testing.
- Neurological examination.
- Eye tests.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Electromyogram (EMG)a diagnostic procedure used to measure the response of nerves and skeletal muscles to electrical activity.
- Nerve conduction study.
- Biopsyremoval of a section of tissue to analyse for cancer cells.