- Nerve tumors, known as neurofibromas or plexiform neurofibromas. These often develop on or under the skin, or from nerves anywhere in the body.
- Central nervous system tumors. These may form on the optic nerve, which connects the eye to the brain, or they may form in other parts of the brain.
- Adrenal gland tumors, known as pheochromocytomas. The adrenal glands are located on top of each kidney, and they produce important hormones.
- Blood cancer (leukemia).
- Digestive tract tumors, known as gastrointestinal stromal tumors.
Neurofibromatosis Type 1 is hereditary, which means it can be passed from parents to children in a family. However, the severity of the condition and which body areas are affected can vary from person to person.
Neurofibromatosis Type 1 is caused by changes in a gene known as NF1. Genes carry information telling cells in the body how to work. The NF1 gene helps to control how and when cells grow, divide, and die.
Most people without Neurofibromatosis Type 1 carry two working copies of the NF1 gene in their cells. One copy of NF1 is inherited from each parent. Cells from people with Neurofibromatosis Type 1 carry one working copy of NF1 and one copy that is changed. This change causes the gene to not work right. It is called an NF1 variant.
About half of children with Neurofibromatosis Type 1 inherit the NF1 gene variant from a parent who also has the syndrome. The other half of children with Neurofibromatosis Type 1 have a new NF1 variant that did not come from a parent. These children have no history of the syndrome in their family. In these cases, the change either happened in an egg or sperm cell that formed the child or in one of the child’s cells during pregnancy. These children are the first in their families to have Neurofibromatosis Type 1. No matter how they acquired the NF1 variant, people with Neurofibromatosis Type 1 have a 50% (or 1 in 2) chance of passing it on to their children.
As people with Neurofibromatosis Type 1 get older, the remaining working copy of NF1 often becomes changed in some of their cells. When both copies of the gene are changed, tumors (which may or may not be cancerous) can develop. Researchers believe this is why people with Neurofibromatosis Type 1 have a higher risk of developing tumors than people who do not have the disorder.
A doctor may suspect this diagnosis based on physical exam and/or after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.
Diagnosing this syndrome is usually done by sequencing the NF1 gene to find variants (gene changes).
Genetic testing does not always find a variant that is responsible for the syndrome. A person can still have the syndrome even if no variants are found.
The diagnosis may be made based on the following clinical information alone:
- Six or more café-au-lait spots measuring at least:
- Five millimeters across at the widest point in children
- Fifteen millimeters across at the widest point in adolescents and adults
- Two or more neurofibromas or one plexiform neurofibroma (a thick, irregular neurofibroma that usually involves multiple nerves)
- Freckles in the armpits or the groin area
- An optic glioma tumor
- Two or more Lisch nodules (small growths in the colored part of the eye known as the iris)
- Specific bone problems, such as abnormality in a skull bone or thinning of the long bones
- A first-degree relative (parent, sibling, child) with a diagnosis of Neurofibromatosis Type 1
Nearly all people with Neurofibromatosis Type 1 develop non-cancerous neurofibromas. They usually start to appear in late childhood and adolescence, and they can continue to develop throughout life. Many women with Neurofibromatosis Type 1 experience a rapid increase in the number and size of neurofibromas during pregnancy.
The total number of neurofibromas seen in adults with Neurofibromatosis Type 1 varies from a few to hundreds or even thousands. Even though most neurofibromas are not cancerous, they can grow to a large size. This may cause pain, nerve damage, or disfigurement. Some neurofibromas become cancerous over time. About 10% (1 in 10) of people with Neurofibromatosis Type 1 will develop a cancerous neurofibroma, also called a malignant peripheral nerve sheath tumor.
People with Neurofibromatosis Type 1 may develop tumors of the central nervous system. The two most common central nervous system tumors in people with Neurofibromatosis Type 1 are optic gliomas and brain tumors. About 20% (1 in 5) of children with Neurofibromatosis Type 1 develop optic gliomas, which usually develop in childhood. They often do not cause any symptoms, even into adulthood. About 3% (about 1 in 25) of people with Neurofibromatosis Type 1 develop brain tumors, such as gliomas. Brain tumors are more likely to develop in people who have optic gliomas.
Women with Neurofibromatosis Type 1 have a slightly higher risk of developing breast cancer under 50 years old than women without Neurofibromatosis Type 1. After age 50, the risk is the same for women with and without Neurofibromatosis Type 1.
People with Neurofibromatosis Type 1 have a higher risk of developing certain other cancers than people without the disorder. However, the overall risk is still very low. These cancers include adrenal gland tumors (pheochromocytomas), blood cancer (leukemia), and digestive tract tumors (gastrointestinal stromal tumors).
Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.
Other ideas to reduce the risk of cancer include:
- Eat a healthful diet with lots of fruits and vegetables
- Get regular exercise
- Avoid smoking or using tobacco products
- Avoid secondhand smoke
- Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
- Get medical attention for unusual or ongoing symptoms
Neurofibromatosis Type 1 can affect many areas of the body. The following are seen in some, but not all people who have Neurofibromatosis Type 1:
- Café au lait spots (smooth, dark, flat birthmarks)
- Freckles in groin, underarms, and under breasts
- Benign growths on the iris, the colored part of the eye (Lisch nodules)
- Learning disabilities
- Autism spectrum
- Larger-than-expected head size
- Abnormal skeletal growth, curved spine (scoliosis), and bowing of the legs
- High blood pressure and blood vessel disorders
- Heart defects
Because of the medical concerns related to this syndrome, specialists in the following areas may need to assess a child with Neurofibromatosis Type 1:
- Neurology
- Ophthalmology
- Dermatology
- Cardiology
- Developmental pediatrician
- Orthopedics
Resources about Neurofibromatosis Type 1:
- Genetics Home Reference (ghr.nlm.nih.gov/condition/neurofibromatosis-type-1)
- Health Supervision for Children with NF1 (https://pediatrics.aappublications.org/content/143/5/e20190660#sec-2)
- Neurofibromatosis Network (www.nfnetwork.org)
- Children’s Tumor Foundation (www.ctf.org)
Other resources:
- Making Sense of Your Genes: A Guide to Genetic Counseling (ncbi.nlm.nih.gov/books/NBK115508/)
Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program