Neurofibromatosis

Neurofibromatosis is a genetic condition that affects the skin, soft tissue, bone, and nervous system. It is characterised by the development of soft tumours called neurofibromas that develop on the nerves and brain or grow on or under the skin.

As they grow, the tumours can press on important areas in the body, affecting the way the body functions with varying degrees of severity. Neurofibromas are usually non-cancerous but in a small percentage of cases may become cancerous.

Types of neurofibromatosis

As neurofibromatosis is a genetic condition, it can be passed from a parent to their child. However, about half of all cases are due to new mutations of the genes that are not inherited from the parents.

There are two distinct types of neurofibromatosis:

NF 1 (Neurofibromatosis 1)

This type represents about 90% of all neurofibromatosis cases and is estimated to affect one in 3,000 New Zealanders. NF 1 is also known as von Recklinghausen disease.

It is characterised by:

• Café-au-lait (‘coffee with milk’) spots (light brown patches on the skin)

• Multiple neurofibromas

• Freckling on the skin under the armpits and in skin folds eg: the groin

• Tiny tumours in the iris of the eye (Lisch nodules).

NF 1 is usually diagnosed in infancy or early childhood.

NF 2 (Neurofibromatosis 2)

This type represents about 10% of all neurofibromatosis cases and is estimated to affect one in 25,000 New Zealanders. NF 2 is also known as bilateral acoustic neurofibromatosis. It is characterised by tumours growing on the auditory nerves, which can affect hearing and balance. NF 2 is usually diagnosed in late adolescence or the early 20s.

Signs and symptoms

The severity of the condition varies greatly from person to person. Some people are barely affected by the condition while others are severely disabled by it.

NF 1

Approximately 60% of people with NF 1 will have only relatively mild signs and symptoms. The most obvious signs of NF 1 are those that affect the skin — café-au-lait spots, freckling, and neurofibromas of the skin. Café-au-lait spots usually measure at least 5mm in diameter in children and can grow to 15mm in diameter in adults.

Neurofibromas are the hallmark of NF 1. There are four main types of neurofibromas, each classified by where they develop in the body. Cutaneous neurofibromas are superficial, soft tumours that grow on the surface of the skin. Subcutaneous neurofibromas grow within the skin layers and can cause local tenderness. The other two types, called nodular plexiform and diffuse plexiform, develop within the body and can cause problems such as:

• Curvature of the spine (scoliosis)

• Malformation of the long bones below the knee and elbow

• Vision loss

• Bleeding or blockage in the gut

• Seizures

• Hydrocephalus (accumulation of fluid on the brain)

• High blood pressure.

Children with NF 1 have high rates of speech impairment, learning difficulties, and attention deficit hyperactivity disorder (ADHD). Puberty may be early or delayed.

Some cancers occur more commonly in people with NF 1. These include some malignant brain tumours, leukaemia, and cancers of the muscles, kidneys and adrenal glands.

NF 2

NF 2 has fewer outward signs than NF 1; in particular, an absence of café-au-lait spots. The first sign of NF 2 is usually progressive hearing loss. This is caused by tumours developing on the eighth cranial nerve responsible for balance and hearing.

Other symptoms can include:

• Ringing in the ears (tinnitus).

• Facial pain or weakness.

• Difficulties with balance.

• Uncoordinated walking.

With NF 2, tumours can also develop on the brain and spinal cord, which can cause symptoms such as seizures. People with NF 2 are also prone to develop cataracts at an unusually young age.

Diagnosis

A diagnosis of neurofibromatosis is based on the characteristic signs of the condition and certain diagnostic criteria.

For a diagnosis of NF 1 to be made, two or more of the following signs need to be present:

• Six or more café-au-lait spots larger than 5mm in diameter

• Two or more neurofibromas

• Freckling under the arm or around the groin

• Lisch nodules

• A tumour on the optic nerve

• Certain abnormalities of the skeleton

• A family member with NF 1.

To diagnose NF 2, tests will be done to check for hearing loss and the presence of tumours in the nerves of the ears, spinal cord, or brain.

Diagnostic tests that may be used in the diagnosis of neurofibromatosis include:

• MRI scans — to screen for tumours and identify changes in the brain.

• X-rays — to identify bone problems.

• Hearing tests.

• Vision tests.

• Electroencephalogram (EEG) — a recording of electrical activity in the brain.

Treatment

As neurofibromatosis cannot be cured, the goal is to monitor the condition and intervene when treatment is required to reduce symptoms and complications. As a general rule, tumours that do not cause any problems are usually left alone.

If treatment is required, it usually involves surgical removal of tumours. Surgical removal may be performed if:

• Tumours cause discomfort and pain

• Tumours keep getting irritated or damaged.

• Tumours in the spine or brain are causing symptoms.

• Sensation or motor function is affected.

• A tumour is suspected, or known, to be cancerous.

Skeletal abnormalities, such as scoliosis, may also require surgical treatment.

If tumours are disfiguring, plastic surgery can help to improve cosmetic looks. Physiotherapy can be useful if mobility or function is affected. If there are deformities of the feet and/or legs orthopaedic devices can also help to improve mobility.

Some brain tumours or tumours along the nerves can be treated with chemotherapy or radiotherapy.

People with neurofibromatosis should have regular physical and neurological examinations. Attention should be given to monitoring changes in the size or number of neurofibromas. Blood pressure should be checked regularly and high blood pressure treated promptly if detected. Annual eye examinations are important for early detection of optic nerve tumours. For people who have NF 2, function of the acoustic nerve and hearing will be monitored.

References

Anderson, J.L. (2015). Neurofibromatosis type 1. Handb Clin Neurol. 2015;132:75–86.
Evans, D.G. (2015). Neurofibromatosis type 2. Handb Clin Neurol. 2015;132:87–96.
Grip, K.W. (2019). Neurofibromatosis type 1 (Web Page). In KidsHealth. Jacksonville, FL: The Nemours Foundation. https://kidshealth.org/en/parents/nf.html [Accessed: 24/11/20]
Hsieh, D.T. (2920). Neurofibromatosis type 1 (Web Page). Medscape Drugs and Diseases. New York, NY: WebMD LLC. https://emedicine.medscape.com/article/1177266-overview [Accessed: 24/11/20]
Hsieh, D.T. (2018). Neurofibromatosis type 2 (Web Page). Medscape Drugs and Diseases. New York, NY: WebMD LLC. https://emedicine.medscape.com/article/1178283-overview [Accessed: 24/11/20]
DermNet New Zealand (2017). Neurofibromatosis (Web Page). Hamilton: New Zealand Dermatological Society. https://www.dermnetnz.org/topics/neurofibromatosis/ [Accessed: 24/11/20]

Last Reviewed: December 2020

Go to our Medical Library Index Page to find information on other medical conditions.