Neurofibromatosis

Types of neurofibromatosis

All are autosomal dominant: a parent with the condition has a 50% chance of passing it to each child. About half of people with NF1 have a new (spontaneous) gene change.

Neurofibromatosis type 1 (NF1)

Diagnostic features

NF1 is diagnosed when 2 or more of these are present (or 1 with a parent who has NF1):

• 6 or more cafe-au-lait spots (over 5 mm before puberty, over 15 mm after)
• freckling in the armpits or groin
• 2 or more cutaneous neurofibromas, or 1 plexiform neurofibroma
• optic pathway glioma
• 2 or more Lisch nodules (harmless spots on the iris) or choroidal abnormalities
• distinctive bone changes, such as bowing of the shin bone or sphenoid wing dysplasia
• a pathogenic NF1 gene variant

Other features

• learning disabilities and ADHD in about half of children
• short stature and large head size
• scoliosis
• high blood pressure, sometimes from renal artery narrowing or pheochromocytoma
• higher risk of certain cancers: malignant peripheral nerve sheath tumor (MPNST), breast cancer in women under 50, gliomas, GIST, leukemia in children

NF2-related schwannomatosis

• bilateral vestibular schwannomas (acoustic neuromas), causing gradual hearing loss, ringing in the ears and balance problems
• meningiomas of the brain and spine
• spinal tumors causing weakness or numbness
• early cataracts
• skin schwannomas

Schwannomatosis

Multiple schwannomas on spinal and peripheral nerves, usually without vestibular tumors. The main symptom is chronic, sometimes severe, pain.

Diagnosis

• clinical examination of the skin, eyes, spine and nervous system
• genetic testing of blood, or of tumor tissue in some cases
• eye exams in children with NF1 yearly to detect optic gliomas
• MRI of the brain and spine when symptoms suggest tumors, and regularly in NF2
• hearing tests in NF2
• whole-body MRI in some centers to measure tumor burden

Treatment

There is no cure, but treatment addresses symptoms and complications.

NF1

• Monitoring: yearly checkups with skin, eye, blood pressure, growth, development and spine reviews.
• Plexiform neurofibromas: MEK inhibitors such as selumetinib (approved for children) and mirdametinib (approved for children and adults) can shrink inoperable tumors. Surgery for selected tumors.
• Cutaneous neurofibromas: removal by surgery or laser if painful or bothersome.
• Optic gliomas: observation; chemotherapy if vision declines.
• Learning support: early educational assessment, individualized education plans, ADHD treatment.
• Cancer surveillance: for example, earlier breast cancer screening in women with NF1.
• Malignant peripheral nerve sheath tumors: surgery, radiation and chemotherapy.

NF2-related schwannomatosis

• MRI monitoring of tumors
• surgery or stereotactic radiosurgery for growing tumors
• bevacizumab to shrink vestibular schwannomas and preserve hearing in some patients
• hearing aids, cochlear implants or auditory brainstem implants

Schwannomatosis

Pain management and surgical removal of painful tumors.

Outlook

Most people with NF1 live full lives, though life expectancy is somewhat reduced on average, mainly due to cancers and vascular problems. NF2 is more variable; outcomes are improving with earlier diagnosis and new treatments. Genetic counseling helps families understand inheritance and options.

Frequently asked questions

What are the first signs of neurofibromatosis?

In NF1, the first sign is usually multiple flat, light-brown cafe-au-lait spots on the skin, often present at birth or appearing in the first year. Freckling in the armpits or groin follows in early childhood. NF2 usually first appears as hearing loss or ringing in the ears in the teens or twenties.

Is neurofibromatosis cancer?

Neurofibromatosis is not cancer, and most of its tumors are benign. However, people with NF1 have a higher lifetime risk of certain cancers, including malignant peripheral nerve sheath tumors, breast cancer and gliomas, so regular monitoring is important.

How is neurofibromatosis inherited?

It is autosomal dominant: a person with NF has a 50% chance of passing it to each child. About half of cases arise from a new genetic change, so there may be no family history. Severity varies widely, even within a family.

Can neurofibromas be removed?

Yes. Skin neurofibromas can be removed by surgery or laser if they are painful, catch on clothing or are cosmetically troublesome, though new ones may appear. Plexiform neurofibromas are harder to remove; MEK inhibitor medicines can shrink them.