Neurofibromatosis Type 1 (NF1)

Overview

Neurofibromatosis type 1 (NF1) is a genetic condition that affects how cells grow along the nervous system. It causes benign (noncancerous) tumors called neurofibromas to form on or under the skin and along nerves throughout the body, and it produces characteristic flat brown skin patches known as cafe-au-lait spots.

NF1 is one of the most common inherited neurological conditions. It is present from birth, though some features appear gradually during childhood and adolescence. The condition varies widely: many people have mild skin findings and lead full, healthy lives, while others develop complications that need ongoing monitoring. NF1 is caused by changes in the NF1 gene, which normally helps keep cell growth in check.

Symptoms

Signs of NF1 often emerge in a recognizable order during childhood. Common features include:

• Cafe-au-lait spots: Flat, light-to-dark brown patches on the skin, usually present from infancy and increasing in number over time.
• Neurofibromas: Soft, fleshy bumps on or under the skin that typically appear in late childhood, adolescence, or adulthood.
• Freckling: Clusters of freckles in unusual areas such as the armpits or groin.
• Lisch nodules: Tiny harmless growths on the colored part of the eye, seen during an eye exam.
• Bone changes: Curvature of the spine (scoliosis) or bowing of the lower leg bones.

Some children also have learning difficulties, attention problems, or a larger-than-average head size.

Causes

NF1 is caused by a change (mutation) in the NF1 gene, which provides instructions for making a protein called neurofibromin. Neurofibromin acts as a brake on cell growth, and when the gene does not work properly, cells along nerves can grow too freely and form tumors.

The condition is inherited in an autosomal dominant pattern, meaning a child needs only one altered copy of the gene to be affected. About half of people with NF1 inherit it from a parent, while the other half have a brand-new mutation that occurred spontaneously, with no family history.

Risk Factors

• Having a parent with NF1, which gives each child a 50 percent chance of inheriting the condition
• A new spontaneous mutation, which can occur with no family history

NF1 affects all ethnic groups and both sexes equally. It is not caused by anything a parent did before or during pregnancy, and it cannot be caught from another person.

Diagnosis

Doctors usually diagnose NF1 based on a combination of physical findings rather than a single test. A diagnosis is made when several established clinical features are present, such as multiple cafe-au-lait spots, freckling in skin folds, neurofibromas, Lisch nodules, certain bone changes, or a first-degree relative with NF1.

• Physical and eye examination: To count cafe-au-lait spots and look for neurofibromas and Lisch nodules.
• Imaging: MRI or other scans if tumors along deeper nerves or in the brain are suspected.
• Genetic testing: Can confirm the diagnosis, especially in young children whose features are not yet fully developed.

Treatment

There is no cure for NF1, so care focuses on monitoring for complications and treating problems as they arise. A team approach often works best.

• Regular checkups: Routine examinations track skin changes, blood pressure, vision, spine alignment, and growth.
• Surgery: Neurofibromas that cause pain, interfere with function, or are cosmetically distressing can sometimes be removed.
• Targeted medication: Certain medicines are now used for some plexiform neurofibromas that cannot be removed surgically.
• Supportive care: Educational support for learning difficulties and management of scoliosis or other bone issues.

Because a small number of tumors can become cancerous over time, any neurofibroma that grows rapidly, becomes painful, or changes in feel should be evaluated promptly.

When to See a Doctor

See a doctor if a child has several cafe-au-lait spots, unusual freckling, or soft skin lumps, so the condition can be assessed. If NF1 is already diagnosed, contact a clinician promptly for:

• A lump that grows quickly, becomes hard, or turns painful
• New or worsening weakness, numbness, or loss of function
• Persistent headaches or vision changes
• A new curve of the spine or bowing of a leg

Sudden severe weakness, loss of bladder or bowel control, or sudden vision loss warrant urgent medical attention.

Related Topics

Frequently Asked Questions

References

1. National Institute of Neurological Disorders and Stroke (NINDS). Neurofibromatosis.
2. MedlinePlus, U.S. National Library of Medicine. Neurofibromatosis type 1.
3. Mayo Clinic. Neurofibromatosis — Symptoms and causes.
4. National Cancer Institute (NCI). Neurofibromatosis.