Neurofibromatosis type 1

Overview

Neurofibromatosis type 1 (NF1) is a genetic condition that causes changes in skin pigment and tumors on nerve tissue. Skin changes include flat, light brown spots and freckles in the armpits and groin. Tumors can grow anywhere in the nervous system, including the brain, spinal cord and nerves. NF1 is rare. About 1 in 2,500 is affected by NF1.

The tumors often are not cancerous, known as benign tumors. But sometimes they can become cancerous. Symptoms often are mild. But complications can occur and may include trouble with learning, heart and blood vessel conditions, vision loss, and pain.

Treatment focuses on supporting healthy growth and development in children and early management of complications. If NF1 causes large tumors or tumors that press on a nerve, surgery can reduce symptoms. A newer medicine is available to treat tumors in children, and other new treatments are being developed.

Symptoms

Neurofibromatosis type 1 (NF1) usually is diagnosed during childhood. Symptoms are seen at birth or shortly afterward and almost always by age 10. Symptoms tend to be mild to moderate, but they can vary from person to person.

Symptoms include:

• Flat, light brown spots on the skin, known as cafe au lait spots. These harmless spots are common in many people. But having more than six cafe au lait spots suggests NF1. They often are present at birth or appear during the first years of life. After childhood, new spots stop appearing.
• Freckling in the armpits or groin area. Freckling often appears by ages 3 to 5. Freckles are smaller than cafe au lait spots and tend to occur in clusters in skin folds.
• Tiny bumps on the iris of the eye, known as Lisch nodules. These nodules can't easily be seen and don't affect vision.
• Soft, pea-sized bumps on or under the skin called neurofibromas. These benign tumors usually grow in or under the skin but can also grow inside the body. A growth that involves many nerves is called a plexiform neurofibroma. Plexiform neurofibromas, when located on the face, can cause disfigurement. Neurofibromas may increase in number with age.
• Bone changes. Changes in bone development and low bone mineral density can cause bones to form in an irregular way. People with NF1 may have a curved spine, known as scoliosis, or a bowed lower leg.
• Tumor on the nerve that connects the eye to the brain, called an optic pathway glioma. This tumor usually appears by age 3. The tumor rarely appears in late childhood and among teenagers, and almost never in adults.
• Learning disabilities. It's common for children with NF1 to have some trouble with learning. Often there is a specific learning disability, such as trouble with reading or math. Attention-deficit/hyperactivity disorder (ADHD) and speech delay also are common.
• Larger than average head size. Children with NF1 tend to have a larger than average head size due to increased brain volume.
• Short stature. Children who have NF1 often are below average in height.

When to see a doctor

See a healthcare professional if your child has symptoms of neurofibromatosis type 1. The tumors are often not cancerous and are slow growing, but complications can be managed. If your child has a plexiform neurofibroma, a medicine is available to treat it.

Causes

Neurofibromatosis type 1 is caused by an altered gene that either is passed down by a parent or occurs at conception.

The NF1 gene is located on chromosome 17. This gene produces a protein called neurofibromin that helps regulate cell growth. When the gene is altered, it causes a loss of neurofibromin. This allows cells to grow without control.

Risk factors

The biggest risk factor for neurofibromatosis type 1 (NF1) is a family history. For about half of people who have NF1, the disease was passed down from a parent. People who have NF1 and whose relatives aren't affected are likely to have a new change to a gene.

NF1 has an autosomal dominant inheritance pattern. This means that any child of a parent who is affected by the disease has a 50% chance of having the altered gene.

Complications

Complications of neurofibromatosis type 1 (NF1) vary, even within the same family. Generally, complications occur when tumors affect nerve tissue or press on internal organs.

Complications of NF1 include:

• Neurological symptoms. Trouble with learning and thinking are the most common neurological symptoms associated with NF1. Less common complications include epilepsy and the buildup of excess fluid in the brain.
• Concerns with appearance. Visible signs of NF1 can include widespread cafe au lait spots, many neurofibromas in the facial area or large neurofibromas. In some people this can cause anxiety and emotional distress, even if they're not medically serious.
• Skeletal symptoms. Some children have bones that didn't form as usual. This can cause bowing of the legs and fractures that sometimes don't heal. NF1 can cause curvature of the spine, known as scoliosis, that may need bracing or surgery. NF1 also is associated with lower bone mineral density, which increases the risk of weak bones, known as osteoporosis.
• Changes in vision. Sometimes a tumor called an optic pathway glioma develops on the optic nerve. When this happens, it can affect vision.
• Increase in symptoms during times of hormonal change. Hormonal changes associated with puberty or pregnancy might cause an increase in neurofibromas. Most people who have NF1 have healthy pregnancies but will likely need monitoring by an obstetrician who is familiar with NF1.
• Cardiovascular symptoms. People who have NF1 have an increased risk of high blood pressure and may develop blood vessel conditions.
• Trouble breathing. Rarely, plexiform neurofibromas can put pressure on the airway.
• Cancer. Some people who have NF1 develop cancerous tumors. These usually arise from neurofibromas under the skin or from plexiform neurofibromas. People who have NF1 also have a higher risk of other forms of cancer. They include breast cancer, leukemia, colorectal cancer, brain tumors and some types of soft tissue cancer. Screening for breast cancer should begin earlier, at age 30, for women with NF1 compared to the general population.
• Benign adrenal gland tumor, known as a pheochromocytoma. This noncancerous tumor produces hormones that raise your blood pressure. Surgery often is needed to remove it.