Definition and Overview

Neurofibroma refers to a benign, slow-growing, and painless tumour on the peripheral nerve sheath. A person can have one or more of these tumours, which can grow in any part of the nervous system including the brain, nerves, and spinal cord. Thus, a person can have a dermal neurofibroma, spinal neurofibroma, or plexiform neurofibroma.

  • Dermal or cutaneous neurofibroma - A neurofibroma tumour of the skin

  • Spinal neurofibroma - A neurofibroma tumour that develops on the spine, which accounts for up to 38% of all neurofibroma 1 cases

  • Plexiform neurofibroma - A rarer type of neurofibroma that grows on the peripheral nerves

Causes of Condition

Neurofibroma is caused by genetic defects or mutations that either occur spontaneously at conception or are passed down from a parent. The disorder can occur in different types depending on which specific gene is involved. Each type produces different symptoms and they vary in severity.

The three types of neurofibromatosis are:

  • Neurofibromatosis 1 - This condition can occur as early as infancy up to age 10. It is caused by the NF1 gene on chromosome 17. When this gene mutates, it causes the loss of neurofibromin (the protein that regulates cell growth), causing cells to grow uncontrollably.

  • Neurofibromatosis 2 - Occurs in the late teen and early adult years. It is less common than NF 1 and is caused by a mutation of the NF2 gene on chromosome 22. The NF2 gene is responsible for producing the protein merlin. When this gene mutates, it loses its ability to produce merlin properly, causing uncontrolled cell growth.

  • Schwannomatosis - This is the rarest type of neurofibromatosis. It usually affects people 20 years and older. It can be caused by two different gene mutations that affect the Schwann cells, which are responsible for producing the insulating sheath of all the nerves surrounding the brain and the spinal cord.

Certain factors may increase a person’s risk of developing neurofibroma tumours. These include a family history of neurofibromatosis. Both NF1 and NF2 are considered autosomal dominant disorders. Any child of a parent with the condition has a 50% chance of developing the same genetic mutation that caused the tumour to grow. However, this risk is lower (around 15%) for a child whose parent is diagnosed with schwannomatosis.

Key Symptoms

Neurofibromatosis can cause varying symptoms depending on its specific type. In general, however, patients develop painless, slow-growing tumours.

Neurofibromatosis 1 symptoms include:

1.) Café au lait spots or flat, light brown spots that present at birth or appear during the first years of life - Patients with six or more of these spots are likely to have neurofibromatosis 1.

2.) Freckles in the groin or armpits - Young patients aged 3 to 5 with unusual freckles in the armpit and groin area may have NF1.

3.) Lisch nodules or tiny bumps on the iris

4.) Soft bumps on or under the skin

5.) Bone deformities - These may cause a curved spine or a bowed leg

6.) Optic glioma or tumour on the optic nerve

7.) Increased brain volume, which may cause patients to have a head that’s larger than normal

8.) Short stature

9.) Visible signs of the tumour, such as large lumps

Neurofibromatosis 2 symptoms include:

1.) Acoustic neuromas, or benign tumours in both ears - These tumours form on the nerves that carry sound and balance information to the brain. Thus, patients tend to experience related symptoms such as:

  • Hearing impairment, which can range from partial to total hearing loss

  • Ringing in the ears

  • Poor balance

2.) Numbness of the arms or legs

3.) Pain

4.) Facial nerve damage that causes facial drop

5.) Cataracts or other vision problems

6.) Meningiomas – These are multiple benign tumours on the brain and spine that may require frequent tumour removal surgeries.

Schwannomatosis symptoms include:

1.) Chronic pain - The pain associated with schwannomatosis is sometimes so severe and debilitating that patients need to be treated by a pain specialist.

2.) Muscle loss

3.) Numbness or weakness in different body parts

4.) Neurofibroma tumours can sometimes cause various complications especially when they press on some nerves. Thus, patients may also experience other symptoms, such as:

5.) Vision loss

6.) Learning difficulties

7.) Cardiovascular issues

8.) Attention deficit hyperactivity disorder (ADHD)

9.) Hormonal issues, especially during times of hormonal change such as during pregnancy

Patients who develop any of the above symptoms should consult with a doctor. Although it is not considered an emergency, the early detection of the tumour can help prevent more severe symptoms and complications.

Due to the wide range of potential symptoms associated with neurofibroma, patients typically need to undergo various eye and ear exams as well as imaging scans before getting a diagnosis. Once diagnosed, doctors perform various genetic tests to identify the specific type of neurofibromatosis that the patient is suffering from.

Who to See and Types of Treatments Available

Due to the different types of neurofibromatosis, there are many specialties involved in the treatment of the disorder. Patients may need to be treated by a dermatologist (for plexiform neurofibroma treatment) and neurologist or neurosurgeon as well as an oncologist, ophthalmologist, otorhinolaryngology or ENT specialist, and orthopedic surgeon. Since patients are mostly young, paediatricians are also usually involved throughout the treatment process.

Neurofibroma treatment options include:

  • Stereotactic radiosurgery - This is a special medical procedure that delivers radiation directly to the tumour. It is a minimally invasive procedure because it does not require an incision. When performed on patients with NF2, this procedure can help prevent hearing loss.

  • Neurofibroma removal surgery - Performed if a neurofibroma tumour presses on a nerve and causes symptoms.

  • Medications - These mainly involve medications to help relieve the pain caused by the tumour. This is an especially important part of treatment for patients with schwannomatosis. Medications typically include gabapentin, pregabalin, or tricyclic antidepressants.

  • Plexiform neurofibroma resection - Plexiform neurofibroma may require special treatment such as surgical resection, especially if they grow too big.

If a patient has lost his hearing due to neurofibromatosis, he or she may also require auditory brainstem and cochlear implants to help improve or restore hearing.

References:

  • Tonsgard JH. “Neurofibromas.” http://www.nfmidwest.org/wp-content/uploads/2016/03/Neurofibromas.pdf

  • Gerber PA, Antal AS, Neumann NJ, Homey B, Matuschek C, Peiper M, Budach W, Bolke E. “Neurofibromatosis.” European Journal of Medical Research. 2009; 14:102. https://eurjmedres.biomedcentral.com/articles/10.1186/2047-783X-14-3-102

  • Woodruff JM. “Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis.” American Journal of Medical Genetics. 1999 March 26. http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-8628(19990326)89:1%3C23::AID-AJMG6%3E3.0.CO;2-%23/abstract

  • Ferner RE, Huson SM, Thomas N, Moss C, et al. “Guidelines for the diagnosis and management of individuals with neurofibromatosis 1.” J Med Genet. 2007 Feb; 44(2): 81-88. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598063/

  • Velez R, Barrera-Ochoa S, Barastegui D, et al. “Multidisciplinary management of a giant plexiform neurofibroma by double sequential preoperative embolization and surgical resection.” Case Reports in Neurological Medicine. Volume 2013 (2013), Article ID 987623, 8 pages. http://dx.doi.org/10.1155/2013/987623

Share This Information: