Children's Hospital Colorado


What is neurofibromatosis (NF1)?

Neurofibromatosis type 1 (also known as NF1 or von Recklinghausen disease) is a genetic condition. It causes non-cancerous growths (tumors) to develop on any nerve ending throughout the body. NF1 is hereditary and runs in families. Symptoms usually appear in childhood.

The severity of neurofibromatosis can range from having very few signs or medical concerns to having many signs with significant long-term medical issues.

What's the difference between NF1 and NF2?

NF1 is a distinct condition from neurofibromatosis type 2 (NF2), with different signs and symptoms. Although both conditions have similar names, an individual with NF1 is not at risk of developing NF2.

What causes neurofibromatosis?

NF1 is caused by a change (mutation) in the NF1 gene on chromosome 17. Each person has two copies of this gene, with one copy inherited from each parent. Normally, the gene prevents too much growth in cells for certain body parts. If one copy of this gene is altered due to a random error or mutation, it cannot function correctly. This ultimately leads to signs of NF1.

Neurofibromatosis is inherited in an autosomal dominant manner, meaning each child of an affected individual has a 50% chance to develop NF1.

Who gets neurofibromatosis?

NF1 is common, occurring in about 1 in 3,000 births. It affects males, females and all ethnic backgrounds equally. However, no two patients with the same NF1 gene mutation are necessarily affected in an identical manner. Even two individuals in the same family can be affected to different degrees, for reasons that doctors don't yet understand.

In approximately half of patients with NF1, the genetic mutation is inherited from a parent who also has symptoms, although they may be mild and undiagnosed. If a parent is affected, each of his or her children has a 50% (or 1 in 2) chance to inherit the gene mutation and develop NF1. All individuals with an NF1 gene mutation will develop signs of NF1, although we cannot predict which signs, when they might develop or the severity.

In the other half of patients with NF1, the gene change occurred sporadically, meaning no other relatives have the condition. There is a small chance of germline mosaicism, meaning the genetic change happened only in the parent's egg or sperm cells, and the parent does not actually have signs of NF1.

What are the signs and symptoms of neurofibromatosis (NF1)?

Freckles and color changes to patches of skin
The most common initial symptoms of neurofibromatosis (a genetic condition that causes non-cancerous growths) are seen on the skin. The earliest signs of NF1 may be café au lait macules and freckling under the arms, in the folds of skin, or in the groin. Café au lait macules (French for "coffee with milk") are patches of skin that are light brown and may be present at birth. More tend to develop over time, but these marks do not cause problems themselves.

Small growths on the skin
Small growths (called neurofibromas) may occur on the surface of the skin or just beneath the skin. These may appear at any time during life and do not typically cause problems because they tend to remain small. Plexiform neurofibromas are a different type of growth that can occur anywhere under the skin or in any part of the body. These growths may be larger and may become cancerous in a small percentage of people.

Eye and bone changes
Clumps of pigment may form in the iris of the eye, but do not affect vision. Sometimes patients with NF1 develop an optic glioma, a growth on the optic nerve, which may affect vision. Abnormal bone development may affect some individuals.

Other common features
Other features may occur in an individual with NF1 but are not used to make a diagnosis. They include: large head size, scoliosis, seizures, learning difficulties, headaches, short stature and high blood pressure. This list does not include all features of NF1, only the most common features.

What tests are used to diagnose neurofibromatosis (NF1)?

Many children are diagnosed with NF1 based on the presence of certain physical features. Criteria include the presence of at least six café-au-lait macules, freckling, ocular signs, presence of neurofibromas and plexiform neurofibromas, bone changes or a diagnosis of NF1 in a relative. Individuals must have two or more of these characteristics to be diagnosed.

An individual with NF1 is not always born with all the features of NF1. Many features develop over time. A genetic test for NF1 is also available when the diagnosis cannot be made based on a clinical exam. During a genetic test, a blood sample is taken and a geneticist looks at DNA from the sample to determine if there is a change within one copy of the NF1 gene that prevents it from functioning properly.

Why choose Children's Hospital Colorado for neurofibromatosis testing?

Our providers in our Neuroscience Institute have years of experience in diagnosing NF1. Because there are other medical conditions with similar features to NF1, we're also very familiar with the signs of these alternative conditions and testing to distinguish between them.

Our laboratory staff are experts at caring for kids during blood draws. We use special topical creams to minimize the discomfort that may be experienced with a blood draw.

How soon can we expect testing results?

The genetic test for NF1 can take up to 8 weeks to receive results. This is the standard turnaround time for many genetic tests.

A positive test result means an individual has a gene mutation in the NF1 gene and will develop signs of NF1, although we cannot determine what signs will develop or when. About 5% of individuals with NF1 have a negative genetic test result, meaning we have not identified a gene change in the NF1 gene but they may later still develop signs of NF1. We follow and treat these patients as though they have NF1 until they are old enough that we feel more confident that they will not develop the condition.

How do providers at Children's Colorado make a diagnosis?

The genetic blood test is routinely offered when NF1 cannot easily be diagnosed from a physical exam. The blood test is also offered to confirm a clinical diagnosis, for family planning and reproductive purposes, or to test other relatives who may be at risk of developing NF1.

How is neurofibromatosis (NF1) treated?

There is no cure for neurofibromatosis because doctors and researchers cannot correct the underlying genetic cause. However, at Children's Colorado, we follow and manage the care of our patients with NF1so that we can quickly address and treat any medical concerns that develop.

Many individuals have an uncomplicated course of NF1 and do not require much additional medical care. Our program follows the American Academy of Pediatrics' guidelines with annual blood pressure checks, monitoring of growth and development, monitoring the spine for scoliosis and annual ophthalmology evaluations in our Eye Clinic. Individuals diagnosed with NF1 and those suspected of having NF1 are seen annually by our team.

Diagnosis and follow-up treatment

The Neurocutaneous Clinic within Clinical Genetics is the diagnostic clinic for NF1. Follow up in our Neurology or Genetics Clinics includes monitoring for potential health and developmental concerns. If a concern is identified, we have specialists in the Eye Clinic, Neuro-Oncology, Orthopedics, Rehabilitation, Neurology and Neuropsychology Departments among others, who can help to manage and treat concerns.

Why choose Children's Colorado for your child's neurofibromatosis treatment?

Physicians in our Program have several decades of combined experience in diagnosing NF1. We offer genetic testing in a conservative and responsible manner with thorough counseling. Every year, we treat several hundred children with NF1, seeing patients from Colorado, New Mexico, Arizona, Nebraska, Wyoming, Montana and South Dakota.

For diagnosed patients with extensive medical involvement, Children's Colorado has a NF multidisciplinary clinic and a NF "mini" multidisciplinary clinic that both use a team-approach for management of NF1. In addition, our Program is a member of the Children's Tumor Foundation and our physicians participate in annual education clinics about NF1.

Resources for neurofibromatosis and non-cancerous tumors