Neurofibromatosis type 1 (also known as Von Recklinghausen’s disease) is a genetic condition with a wide range of symptoms that need a personalized care approach.

What is NF1?

Neurofibromatosis type 1 is a genetic condition caused by a change (pathogenic variant) in the NF1 gene. Most people with NF1 have recognizable symptoms often affecting the skin, eyes and nervous system. NF1 ranges from mild to severe, and can cause more symptoms in some people than in others. Some symptoms don’t need treatment, while others can be worrisome, such as learning challenges or painful tumors, and may need to be monitored and treated.

Although officially a rare disease, NF1 is quite common, affecting an estimated 1 out of 2,600 people worldwide. NF1 affects males and females equally, and shows no preference for race or ethnicity.

Causes and Types of NF1

NF1 occurs when there is a change in the NF1 gene, which is found on chromosome 17. This change can be inherited, or it may occur spontaneously. The inheritance happens though the autosomal dominant inheritance pattern, which means only one parent needs to have the altered NF1 gene. When NF1 is inherited, this is called familial NF1.

About half of people with NF1 inherit the condition from a parent, while the other half have a new (de novo) gene variant.

There are also some people with mosaic NF1, in which only a portion of the cells in the person’s body have the altered NF1 gene. In some people with mosaic NF1, only certain regions of the body show the typical signs or symptoms of NF1.

NF1 Diagnostic Criteria 

A neurofibromatosis type 1 diagnosis is made by using specific diagnostic criteria. The criteria were revised in 2021 and published in a medical journal, with Johns Hopkins neurofibromatosis experts among the authors.

A person who does not have a parent diagnosed with NF1 must meet two or more criteria. A person who has a parent diagnosed with NF must meet one or more criteria.

The simplified criteria include:

• Six or more café-au-lait macules (brown skin spots) of a certain diameter based on age*
• Freckling in the armpit or groin*
• Two or more neurofibromas (nerve tumors) of any type or one plexiform neurofibroma
• Optic pathway glioma (a type of tumor in the eye)
• Two or more iris Lisch nodules (colored spots on the iris of the eye) or two or more abnormalities in the choroid (the vascular layer of the eye)
• Osseous (bony) lesion such as sphenoid dysplasia, bowing of the tibia (long bone in the leg), or a fracture of a long bone that does not heal
• A pathogenic NF1 gene variant confirmed by genetic testing

*At least one of the two (café-au-lait macules or freckling) must be present on both sides of the body.

Based on these complex criteria, NF1 manifestations or symptoms can involve many different parts of the body. That is why confirming a diagnosis of NF1 requires an evaluation by experts from multiple fields, and may require genetic testing coordinated with a genetic counselor specializing in NF. There are also specific strategies for confirming whether a person has familial NF1 or a spontaneous gene change, or if they have the mosaic type.

Genetic Testing for NF1

Genetic testing of the NF1 gene is available and typically uses blood or saliva. It is not always needed for diagnosis. However, it may be useful in several cases by helping:

• Diagnose people who have symptoms of NF1 but do not meet diagnostic criteria.
• Answer questions about inheriting or passing on the altered NF1
• Determine the type of NF1 (familial or spontaneous).
• Get insight about mosaic NF1. This type of testing is more complex and may use the affected tissue instead of or in addition to blood or saliva.

A consultation with a genetic counselor can help determine the appropriate genetic testing approach.

Common NF1 Manifestations (Symptoms) and Treatment Strategies

There are many ways NF1 can manifest, and the symptoms vary among people who have this condition.

Even people in the same family who share an NF1 gene may have different symptoms. Having the signs and symptoms of NF1 does not always mean that they need to be treated. Some manifestations, like café-au-lait spots, are generally harmless and can be left alone. Other manifestations, like certain types of nerve tumors, may need monitoring and, eventually, treatment. In many cases, NF1 symptoms can be effectively managed when working with a comprehensive multispecialty care team.

Common NF1 manifestations and symptoms include:

Cognitive, Developmental and Behavioral Challenges

NF1 commonly affects learning, attention and behavior. These challenges are among the most frequent manifestations of NF1, and they can occur even in people who otherwise have mild physical symptoms. Cognitive and behavioral changes vary widely from person to person. How they affect a person’s function and quality of life may change over time.

Cognitive and developmental challenges common in people with NF1 include:

• Attention-deficit/hyperactivity disorder (ADHD).
• Learning disorders, including difficulties with reading, writing and math.
• Autism spectrum disorder and social communication differences.
• Speech and language disorders.
• Motor (movement) delays, which are related to low muscle tone (hypotonia).
• Executive functioning challenges, including difficulties with planning, organization and working memory.
• Visuospatial challenges, which may affect handwriting, math, navigation and visual organization.
• Anxiety and mood concerns, including increased risk for depression and emotional regulation difficulties.

Severity of these challenges varies. Some people have mild challenges, while others need ongoing and comprehensive support in these areas.

Learning and School Performance

Many children with NF1 fall in the average range when it comes to intellectual abilities. However, they may have specific areas of strength and weakness. Difficulties with attention, executive functioning and visuospatial skills may affect academic performance, organization and daily functioning.

Many of the learning challenges can persist into adulthood. Adults with NF1 may benefit from tailored assessment of the impact on daily function to help understand if treatment is needed.

Evaluation

Comprehensive evaluation of cognitive, developmental and behavioral functions may include:

• Developmental and behavioral assessment
• Neuropsychological evaluation
• Speech and language evaluation
• Occupational and physical therapy assessment
• School-based educational testing

Treatments and Support

Identifying these challenges early allows for targeted treatment strategies. Support at school and at home combined with clinical support from the NF care team can help achieve the best results through the following approaches:

• Educational accommodations such as individualized education programs and 504 plans
• Behavioral therapy
• Speech and language therapy
• Occupational and physical therapy
• Cognitive behavioral therapy (CBT)
• Medication, when appropriate

Because cognitive and behavioral challenges are common in NF1, care from a multispecialty team with expertise in neurodevelopmental differences can help children with NF1 reach their full potential across development, education and daily life.

NF1-Related Tumors

Having NF1 increases a person’s likelihood of tumors developing in the body. Therefore, people with NF1 have a higher risk for benign and malignant tumors (cancers) than people without NF1.

Common types of tumors associated with NF1 include:

• Peripheral nerve sheath tumors
• Gliomas
• Certain cancers

Peripheral Nerve Sheath Tumors

People with NF1 may develop different types of nerve sheath tumors. They usually affect the peripheral nervous system (the nerves that travel from the spine throughout the body). Common peripheral nerve sheath tumors associated with NF1 include:

• Cutaneous neurofibromas 
  • What they are: Nerve sheath tumors in the dermal (middle) layer of the skin. They can vary in size and can cause pain, itching and disfigurement, or may have no symptoms. The number of these tumors is usually low in childhood and grows as people enter their 20s and 30s.
  • Treatment strategies: They can be monitored, removed with surgery or treated via a clinical trial. Researchers are also exploring approaches for preventing these tumors.
• Subcutaneous neurofibromas
  • What they are: Nerve sheath tumors in deeper layers of the skin (in the dermis and below). They generally have less-defined borders than cutaneous neurofibromas.
  • Treatment strategies: No medication is currently available to shrink the tumor, so if it is causing symptoms or rapidly growing, it can be surgically removed.
• Plexiform neurofibromas
  • What they are: Nerve sheath tumors that affect the nerves beneath the skin (the deep nerves). These include nerves along the spinal column, head and neck, as well as nerves in the torso and limbs. About 30%–50% of people with NF1 have plexiform neurofibromas. They tend to grow the most from infancy to late childhood, and slow down in adolescence or adulthood, although it varies from person to person. These tumors can have no symptoms, or they may cause pain or neurologic dysfunction.
  • Treatment strategies: Researchers have been working for decades on ways to prevent, slow or shrink these tumors, as well as ways to improve symptoms. So far, two S. Food and Drug Administration-approved therapies, selumetinib and mirdametinib, are available for children and adults to treat plexiform neurofibromas that cause symptoms.
• Atypical neurofibromas of unknown biologic potential (ANUBP, also called atypical neurofibromas)
  • What they are: These are lesions that often develop within a plexiform neurofibroma and have specific genetic markers that mean the tumor can become malignant (cancerous).
  • Treatment strategies: Atypical neurofibromas are the most recently identified peripheral nerve sheath tumors in people with NF1, and are being actively studied. Current treatment strategies focus on surgical removal when feasible and clinical trials.
• Malignant peripheral nerve sheath tumors (MPNST)
  • What they are: MPNSTs are cancers of the peripheral nerve. While they are rare overall, they can affect as many as 8%–15% of people with NF1. When they develop in a person with NF1, they often develop inside plexiform neurofibromas or ANUBP.
  • Treatment strategies: A major part of routine NF1 care is clinical assessment of a person’s risk for developing an MPNST. Ongoing monitoring can help with prevention or early diagnosis. Treatment may include surgery, radiation and chemotherapy, and requires a multispecialty team of experts.

Gliomas

Common gliomas associated with NF1 include:

• Optic pathway gliomas (OPG)
  • What they are: Low-grade (benign) tumors of the nerve that feeds the eye. They may also affect the brain tissue that communicates with that nerve. OPGs occur in roughly 30% of children with NF1. They are a risk only for children; the risk of developing this tumor lowers as people age.
  • Treatment strategies: Fortunately, most children with OPGs do not need treatment. An important part of pediatric NF1 care is partnership with ophthalmology, because changes in vision or health of the optic nerve could warrant additional evaluations (such as a brain MRI) and, potentially, treatment.
• Non-optic pathway gliomas (NOPGs)
  • What they are: These are nerve tumors located outside of the visual pathway. They are often found in the brainstem or cerebellum (the nerve structures in the middle of the brain). NOPGs can range from low grade (benign) to high grade (cancer). Fortunately, malignant gliomas are very rare in people with NF1, but they do occur more frequently in people with NF1 than the general population.
  • Diagnosis and treatment strategies: NOPGs can be hard to distinguish from focal areas of signal hyperintensity (FASI) — bright spots on a brain MRI that do not need treatment. FASI are common in people with NF1, and fade over time. Distinguishing a FASI from a low-grade glioma can be difficult and requires expert, multispecialty input.

Other Cancers

While people with NF have a higher risk of developing tumors, including cancers, than the general population, the overall likelihood of developing cancer is low. The risk is different for every person with NF1. Your NF1 care team can recommend appropriate screening and evaluations based on your health, type of NF1 and other personal factors.

Some of the cancers that can affect people with NF1 include:

• Breast cancer, especially in women under 40 years old.
• Gastrointestinal stromal tumor (GIST): Tumors in the wall of the stomach or intestines that often do not need treatment in people with NF1, but in some cases may need surgical removal or drug therapy.
• Pheochromocytomas or neuroendocrine tumors: These tumors involve the cells that make a class of hormones called catecholamines. They are very rare in people with NF1, but more common than in people who do not have NF1.
• Juvenile myelomonocytic leukemia: A type of leukemia in children that is very rare but can occur in young children with NF1.

Bone-Related NF1 Manifestations

One of the developmental changes that happen in people with NF1 is related to the health of bones. Common bone-related changes include:

• Low bone density: Bones are less dense than normal.
• Low vitamin D: People with NF1 often need vitamin D supplements.
• Scoliosis (sideways curved spine) and kyphosis (forward curved spine): These conditions need special monitoring to keep an eye on worsening of the curve.

There are also far less common bone changes that occur in people with NF1 that need specialized monitoring and support, including:

• Bowing of the legs: The shin bones (tibia) sometimes grow curved instead of straight. This is most often seen in young children.
• Pseudarthrosis: In some children, a bone (most commonly the lower leg) can fail to heal after a break, forming a false joint (pseudarthrosis). This is a rare but serious condition.
• Skull and facial bone changes: Some people develop differences in skull or facial bones, including sphenoid wing dysplasia (a bone defect near the eye), which can affect the orbit.

Neurologic NF1 Symptoms

These neurologic symptoms can be independent, or they can be related to neurofibromas or gliomas. Some of these symptoms can also be signs of nerve or spinal cord compression — when the tumor presses on the spinal cord.

• Headaches
• Numbness or weakness
• Pain
• Seizures
• Itching
• Sleep problems
• Mental health concerns, including anxiety, depression and low self-esteem
• Delayed or early puberty

Heart and Neurovascular Conditions Related to NF1

Overall, heart and neurovascular conditions related to NF1 are rare. However, if they occur, they are often in children and need monitoring and treatment. Some of the related conditions include:

• Aneurysms
• Coarctation of the aorta 
• Moyamoya disease 
• Renal artery stenosis
• Stroke
• Glaucoma

NF1 and Family Planning

Every person with an NF1 gene change has a 50% chance of passing it on to each child. It does not matter whether the NF1 gene change was inherited or spontaneous.

When planning a pregnancy, it may be helpful for people with NF1 to consult a genetic counselor. The counselor can advise on family planning and testing options. Some people choose in vitro fertilization (IVF) because it allows pre-implantation genetic testing to select embryos without the problematic gene variant. Prenatal genetic testing is another option to test for the gene variant; it is performed on an embryo in the uterus.

Hope for People with NF1

NF1 is a lifelong condition with a wide range of symptoms that can lessen or worsen as the person ages. There are two therapies (selumetinib and mirdametinib) recently approved by the FDA to manage the signs and symptoms of NF1-associated plexiform neurofibromas. Many other therapies, ranging from lifestyle modifications to NF1 gene therapies, are in development for other symptoms and manifestations.

Johns Hopkins is at the forefront of NF1 research, conducted through the Johns Hopkins Comprehensive Neurofibromatosis Center and the Kennedy Krieger Institute Pediatric Neurofibromatosis Program.

Medically reviewed by Jaishri Blakeley, M.D. May 21, 2026.