Neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a genetic condition that causes changes in skin pigment and the growth of 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 children are born with the condition.

The tumors often are not cancerous. These are known as benign tumors. But sometimes they can become cancerous. Although symptoms often are mild, complications can occur. They 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 managing complications in adults and children. If NF1 causes large tumors or tumors that press on a nerve, surgery can reduce symptoms. Medicines can treat tumors that grow along nerves, called plexiform neurofibromas.

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. The iris is the colored part of the eye. These bumps can't easily be seen and don't affect vision.
• Soft, pea-sized bumps on or under the skin called neurofibromas. These noncancerous tumors usually grow in or under the skin but also can grow inside the body. A growth that involves many nerves is called a plexiform neurofibroma. Plexiform neurofibromas can cause visible changes on the face. 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 6. 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. People with NF1 tend to have a larger than average head size due to increased brain volume.
• Short stature. People who have NF1 often are below average in height.

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 multiply.

Autosomal dominant inheritance pattern

In an autosomal dominant disorder, the changed gene is a dominant gene. It's located on one of the nonsex chromosomes, called autosomes. Only one changed gene is needed for someone to be affected by this type of condition. A person with an autosomal dominant condition — in this example, the father — has a 50% chance of having an affected child with one changed gene. The person has a 50% chance of having an unaffected child.

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. However, it's possible to have NF1 without a family history of the condition.

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 related to NF1. Less common complications include epilepsy and the buildup of excess fluid in the brain.
• Worries about appearance. Visible signs of NF1 can include widespread cafe au lait spots, many neurofibromas on the face or large neurofibromas. In some people this can cause anxiety and emotional distress, even if they're not medically serious.
• Skeletal symptoms. Some people 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 linked to 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 during 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 may 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, brain tumors and some types of soft tissue cancer. Screening for breast cancer should begin earlier, at age 30, for women with NF1 compared with the general population.
• Benign adrenal gland tumor, known as a pheochromocytoma. This noncancerous tumor produces hormones that raise blood pressure. Surgery often is needed to remove the tumor.