Neurofibromatosis

We understand that you may have a lot of questions when your child is diagnosed with NF1:

• What is it?
• What does it mean?
• How will it affect my child?

We’ve tried to provide some answers to those questions here, and when you meet with our experts, we can explain your child’s condition and options fully.

What is neurofibromatosis type 1 (NF1)?

Neurofibromatosis type 1 is a genetic condition that can cause a variety of symptoms, including:

• multiple flat, light-brown patches of skin pigment, called café-au-lait macules or spots
• skinfold freckling
• visible neurofibromas that appear as bumps on or under the skin
• small nodules on the iris (colored part of the eye) called Lisch nodules, which do not cause problems. They’re invisible to the naked eye, but can be detected by an ophthalmologist.

What complications are associated with NF1?

Complications of NF1 vary just as much as the symptoms do. Some of the more common complications include:

• Headaches. Children with NF1 often experience headaches. If the frequency or nature of the headaches change, you should contact your doctor.
• Deformation of bone structure, including:
  • scoliosis (curvature of the spine). Scoliosis affects around 10 percent of individuals with NF1, and may appear in early childhood.
  • tibial dysplasia (bowing of the bones of the lower leg). This affects around 3 to 5 percent of people with NF and appears during the first year of life.
• Optic pathway glioma. This is a thickening of the nerve connecting the eye to the brain that affects around 15 percent of people with NF1. Most optic pathway gliomas are incidental findings and don’t affect vision, cause other symptoms or need treatment.
• Malignant changes to plexiform neurofibromas. Around 10 percent of plexiform neurofibromas may become malignant. If your child’s tumors become painful, grow suddenly or otherwise change in appearance, contact your doctor right away.
• Issues with growth and/or puberty development. Some kids with NF1 have problems in these areas. Your child’s doctor will monitor her height, weight and development to make sure that she stays on track.

Can NF1 be cured?

Not yet. Researchers at Children’s Hospital Boston and around the world are working to gain a deeper understanding of the mechanisms behind NF1 in order to develop more effective treatments and a cure. If your child has NF1, she may be eligible to participate in one of our clinical trials.

Will my child be OK?

Most likely yes. While it’s difficult to predict the course of NF1 for any individual child, most people with NF lead healthy, productive lives.

How common is it?

NF1 is far from rare — it occurs in one in 3000 births.

What’s a neurofibroma?

A neurofibroma is a tumor that grows along a nerve in any part of the body. Usually, they look like little rubber balls under the skin, or they may protrude from the skin. They’re usually benign (non-cancerous), and most often appear during puberty and adulthood. A person with NF1 may develop only a few or more — at present, there’s no way to predict how many neurofibromas will develop.

Since neurofibromas are wrapped around nerve fibers, they can sometimes be painful if pressure is applied to them. Neurofibromas can be removed, but the surgery may leave a scar, and the neurofibroma may grow back.

Some children with NF1 may also have plexiform neurofibromas. These are a different kind of neurofibroma and generally present at birth, even though they might not be visible until later. Plexiform neurofibromas may be large, and they can encircle and interweave with normal tissue, making them extremely hard to remove. We monitor these tumors for change in size, consistency or appearance of new symptoms such as pain.

Is it cancer?

Not usually. Neurofibromatosis is characterized by tumors that are mostly benign, but in around 10 percent of individuals, the neurofibromas may have malignant (cancerous) changes.

Is NF1 ever called anything else?

Yes, you may have heard NF1 also referred to as von Recklinghausen's disease.

What’s the difference between neurofibromatosis 1 and neurofibromatosis 2?

Quite a lot — NF2 is a completely different condition:

• It’s caused by mutations of a different gene on a different chromosome.
• It’s much rarer, occurring in one in every 30,000 births.
• The classic symptom of NF2 is hearing loss that begins in the teens or early twenties.

It’s extremely rare that someone would have both NF1 and NF2.

If I have NF1, is my child at additional risk for NF2?

Not at all — since they’re caused by different genes, in terms of heritability, NF1 and NF2 are completely separate.

What is segmental NF? 

Segmental NF is a form of NF1 in which symptoms are limited to a discreet part of the body. 

What’s Schwannomatosis?

Schwannomatosis is a recently-recognized form of NF that is genetically distinct from NF1 and NF2. It occurs rarely.

Who should be screened for NF1?

You should be screened for NF1 if you and/or your child have:

• a family history of NF1 and/or
• multiple brown skin spots, bumps on or under the skin, and/or Lisch nodules
• a crooked arm or leg bone 

Follow-up care will depend on the type and complexity of symptoms, and will be individualized for each person.

How reliable is genetic testing for NF1?

Unfortunately, genetic testing isn’t perfect. In the vast majority of people who show two or more symptoms of NF1 — around 95 percent — genetic testing can identify a mutation. But that means that five percent of people with NF1 will not have a mutation that is identifiable by the testing that is currently available.

As a result, if your child tests negative for a NF1 mutation, there’s still a chance that she could have NF1, and should still be followed if she has at least one known symptom of the condition. Please remember that the results from genetic tests should always be discussed with your doctor or genetic counselor.

Causes

What causes neurofibromatosis 1?

Inheritance of NF1

NF1 is an “autosomal dominant” gene. This means that:

• Even though each child inherits two NF1 genes (one from each parent), if only one of them has a mutation, the child will have the condition.
• If a parent has the mutation, there is a 50% chance that any child of theirs can have it, too.
• It affects males and females equally.

When neurofibromatosis is not inherited

Around half of all individuals with NF1 are the first in their family to have the condition. This usually means that the condition wasn’t inherited from a parent, but instead is the result of a spontaneous mutation of the NF1 gene.

But I thought you said that NF1 was genetic?

It is a common misconception that “genetic” always means “inherited.” In fact, “genetic” only means “caused by a gene,” which can (and often does) mean that a gene is inherited, but it can also mean that the gene mutated spontaneously by itself.

Other causes

There has been absolutely no evidence that NF1 is caused by any environmental agents or by anything that the mother did during pregnancy.

Signs and symptoms

What are the symptoms of NF1?

NF1 can affect different areas of the body and many of the features are age-dependent. In order to be diagnosed with NF1, your child must have at least two of the following symptoms:

Keep in mind that any of these symptoms — even neurofibromas and plexiform neurofibromas — can also appear in people who don’t have NF1.

It’s also important to remember that two people in the same family can both have NF1 but experience different symptoms and levels of severity. It’s impossible to predict how anyone’s NF1 will progress, even by looking at a family member who also has the condition.

FAQ

Q:  Will my child be OK?
A: Most likely yes. While it’s difficult to predict the course of NF for any individual child, most people with NF lead healthy, productive lives.

Q:  Is there a test for NF1?
A: Yes, but it’s not perfect. In patients who already have at least two of the typical clinical signs, genetic testing can identify the mutation that causes NF1 about 95 percent of the time. But because there’s a 5 percent chance that your child may test negative but still have NF1, if she has clinical signs, we will follow her closely regardless of her test result.  

Q:  When will I know whether my child has NF1?
A: It’s hard to say for sure when a child’s symptoms will develop. But we know that 80 to 85% of patients with NF1 are diagnosed by age 6, and 95% are diagnosed by age 8. So if your child is older than 8 and hasn’t developed enough symptoms to be diagnosed, the likeliness of her having NF1 drops dramatically.

Q:  If there’s some uncertainty as to whether my child has NF1, why wouldn’t I just ask for a genetic test?
A: Most of the time, the results of the test don’t matter in a practical sense, because they won’t necessarily change how we approach your child’s care. Since there’s a 5% chance that the test won’t identify a mutation, as long as she shows clinical signs, we’ll follow her, just to be safe.

The tests are also expensive, and not all insurance companies and plans may cover the cost of all the testing that’s needed to make a diagnosis.

That said, some parents choose to have the test anyway. Your doctor or genetic counselor will be happy to discuss all of your options with you.

Q:  Is it possible to know whether my child has NF1 without doing genetic testing?
A: Definitely — in fact, NF is most often diagnosed clinically, and many patients with NF never undergo genetic testing. 

Q: Are neurofibromas contagious?
A: Not at all. NF1 is a genetic disorder, meaning that if your child has it, it was already in her genes when she was born. Neurofibromas don’t “spread” from person to person.

Q: Isn’t neurofibromatosis what the Elephant Man had?
A: No. While scientists thought this was so for many years, in 1986 it was established that Joseph Merrick, the so-called “Elephant Man,” actually had an extraordinarily rare condition called Proteus syndrome.

Q: Are there any dietary modifications that might help my child?
A: Aside from the benefits that a healthful diet, exercise and vitamins offer to everyone, there’s no evidence that they affect the growth of neurofibromas or the progression of neurofibromatosis.

Q:  Did I do anything to cause my child’s neurofibromatosis?
A: No. There is nothing you did (or didn’t do) before or during pregnancy, or after your child was born, that could have caused NF1.

Q: Are the clinical problems treatable?
A: Yes, and your child should be cared for by NF1 specialists who are familiar with treating the condition in children.

Q:  Can we predict how my child’s condition will progress?
A: Unfortunately, NF1 is highly unpredictable. At this time, it’s very difficult to predict whether your child’s symptoms will be mild, moderate or severe. Severe complications are rare.

Q: Is there anything else that can cause these symptoms?
A: Yes, there are some other rare conditions. The doctor will keep them in mind during your child’s visit, and test for them if they seem to be a possibility.

Q: If my child has many café-au-lait spots, does that mean that she will develop very severe NF1?
A: Not necessarily — there’s no connection between the number of café-au-lait spots and the severity of NF1.  

Q: If my child has many café-au-lait spots, does that mean that she’ll develop many neurofibromas?
A: No, all factors of NF1 are independent:

• Many spots don’t mean many neurofibromas.
• Having a spot doesn’t mean that a neurofibroma will grow on that spot.
• A parent and child can both have NF1 but different symptoms and degrees of severity.

Q: Is inherited NF1 more severe than NF1 from a spontaneous mutation?
A: No, there’s no correlation between how your child came to have NF and how mild, moderate or severe her symptoms may be. 

Q: Could I have another child with NF1?
A: Yes, because anyone can have a child with NF1. If you have a mutation in the NF1 gene, there’s a 50 percent chance that another child will have the mutation. If you don’t have the mutation, there’s about a 1 percent chance that another would have NF1, too.

Q: Is there any way to know whether I will have another child with NF1?
A: Prenatal diagnosis is available, although it is not possible to know what symptoms of NF1 a child may have. Talk to your genetic counselor for more information and to discuss testing options in more detail.

Q: Should my other children be tested for NF1?
A: If your other children have any signs of NF1, they should be evaluated.

Q: Is it possible to have NF1 and not know it?
A: It’s certainly possible to have NF1 and have symptoms that are so mild that the person thinks nothing of them. In fact, although it’s rare, a parent may learn that he or she also has NF1 when his or her child is diagnosed.

Q: Should the parents be evaluated for NF1?
A: Yes, if the parent is showing signs or symptoms of NF1.

Q: Will my child be able to have children?
A: Most likely - NF1 doesn’t affect fertility in males or females.

Q: If my child becomes a parent some day, will his children also have NF1?
A: As with anyone with NF1, there’s a 50% chance that his or her child will also have the condition.

Questions to ask your doctor

After your child is diagnosed with neurofibromatosis, you may feel overwhelmed with information. It can be easy to lose track of the questions that occur to you. Lots of parents find it helpful to jot down questions as they arise — that way, when you talk to your child’s doctors, you can be sure that all of your concerns are addressed.

If your child is old enough, you might suggest that she write down some questions to ask her health care providers, too.

Always ask questions about unfamiliar words— feel free to interrupt your child’s doctor to ask what something means, or at any time when you don’t understand something. We know it’s a lot to take in at once, and want to make sure you understand everything you need to. 

Other questions include:

• Can you give me a list of possible problems I should check for, including behavioral, physical and educational issues?
• What aspects of my child’s health and behavior should I be paying attention to?
• How can I explain this to my friends, family and doctors?
• What should I be doing now?
• Which care providers should my child see, and how often?
• What medications will you prescribe, if any? What are the possible side effects?
• Does anything need to change in my child’s home, school or social life?
• Are there any resources you recommend for more information?

Teens and NF1

It can be hard enough to be a teenager without having to deal with a chronic condition like NF1. This is usually when neurofibromas tend to develop, and this can be very upsetting for someone who may be beginning to take a special interest in her appearance. Understandably, both parents and teens want to know when — and how many — neurofibromas will show up, but this is impossible to predict.

There’s also been some evidence that at times of hormonal changes, such as puberty or pregnancy, more symptoms of NF1 may develop. Understanding what your child is going through can help you support her during this important time - and help you cope, too. Your teen may:

• be exploring her own identity - figuring out who she is, what’s important to her and how she can incorporate her condition into how she sees herself and her place in the world
• have a strong desire to feel “normal” and not have anything that makes her feel different from her peers
• resent the need for close monitoring of her health

Here are some ways you can help:

• Encourage your child to talk openly with you. Keep your initial focus on listening to what she’s saying, and making sure you understand what she means. Sometimes what a teen needs most is simply to feel understood.
• Include your teen in decisions about her health care as early as appropriate.
• Encourage your child to find peer support among other NF1 patients. This can decrease her sense of being “different,” and reassure her that what she’s going through is normal.     
• Help your teen to set long-term academic and vocational goals.
• Teens like to feel like active contributors to the family. Encourage your child to do chores and care for younger siblings. Sibling support is also important.
• If appropriate, help your teen identify a trusted adult she can talk with about issues that she may not be comfortable talking to members of her family about.
• Support her efforts to develop and sustain friendships and other social relationships.

Make sure that your teen knows that there are lots of ways to meet — and have fun — with other teens with NF, including summer camps, such as Camp New Friends offered through Neurofibromatosis Inc or the Children’s Tumor Foundation’s NF Summer Camp. CTF also runs a weekly youth-moderated online chat room through a program called YouthCONNECT for kids aged 10-17 who have NF or have a sibling or friend with NF.

NF1 and learning disabilities

Up to half of all children with NF1 have some kind of learning disability, which range from mild to severe. True intellectual disability is rare. And just because a child has difficulties with learning doesn’t mean she’s not smart — it’s been generally shown that the problem with learning disabilities isn’t a lower IQ, but an issue with one or more of the following:

• working memory
• attention
• focus
• visual-motor function (dexterity, fine-motor control)
• spatial orientation (awareness of the body in space)

It’s also widely accepted that the earlier a learning disability is identified, the more effective treatment and compensatory measures tend to be. That’s why we recommend that if your child has had some delayed development (such as with sitting, walking or talking), or if there’s been any suggestion of learning issues at school, you should:

• Ask that your child be evaluated by her school for a learning disability — if a learning disability is identified, the school can then put together an Individualized Education Plan (IEP) for your child to identify and help her meet her educational goals.
• Consider comprehensive neuropsychological testing for your child. Typically, schools do intelligence and basic achievement testing, but they lack the resources to pull out the level of detail that a specialist can provide. If possible, your child should be evaluated by a neuropsychologist who has experience in testing children with NF1.

Can learning disabilities get worse with time?

No, although it might sometimes look that way. Since different things are asked of children at different levels of their education, issues may surface that hadn’t yet been identified. For example, your child may easily learn to read, but have some difficulty when it comes time to interpret what she has read.
 

When resources are available to help my child succeed?

Luckily, there has been lots of research into how kids with different kinds of learning disabilities can learn best. Your child’s IEP team will work with you to develop a plan that’s been customized for her, but adjustments that the school might make could include

• giving your child extra time on tests
• assigning a tutor to work with her
• having her sit closer to the front of the room

Like all children, kids with NF1 have strengths and weaknesses; and like all children, helping them succeed is just a matter of capitalizing on their strengths and compensating for their weaknesses.

How is NF1 diagnosed?

Children can have different pathways to a diagnosis of NF1, but a typical diagnostic process might look like this:

• The pediatrician notices some café-au-lait spots on the child’s skin (these may look to the parent just like birthmarks). These spots may be present at birth, but more commonly they develop through the first few years of life. Since this is one of the diagnostic criteria of NF1, the pediatrician may recommend that the child schedule an evaluation with our Neurofibromatosis Program.   
• Our doctors do a complete and thorough physical exam of the child and take her medical, developmental, history and family history. She may also see an ophthalmologist.

 If your child meets the clinical criteria for diagnosis of NF1 at this time, her doctor will make the diagnosis, and discuss next steps with you. The clinical criteria are that she must have at least two of the following:

If your child doesn’t meet the clinical criteria for diagnosis, her doctor will schedule periodic follow-up visits to see if the symptoms develop. In some cases, the doctor may want to do genetic testing.

Keep in mind that between 80 to 85 percent of children with NF1 are diagnosed by the time they’re 6, and 95 percent are diagnosed by age 8. That means that if your child is older than 8 and hasn’t been diagnosed, the likelihood that she has NF1 drops dramatically.

If there’s some uncertainty as to whether my child has NF1, why wouldn’t I just ask for a genetic test?

Most of the time, the results of the test won’t change how we approach your child’s care. The tests are also expensive, and not all insurance companies and plans may cover the cost.

Your physician and genetic counselor will be happy to discuss all of your options with you.

Can doctors identify neurofibromas just by looking at them?

No, a biopsy is needed to confirm that a bump is a neurofibroma. But most of the time, neurofibromas appear after other symptoms of NF1–such as café-au-lait macules and skinfold freckling–have already been identified. So in a child with NF1, we may assume that a new bump is a neurofibroma.

Can NF1 be diagnosed during pregnancy?

If a parent has NF1 and a known mutation, testing can be performed to determine if the baby has inherited the same mutation. But keep in mind that even if the test shows the mutation, it is difficult to know anything about what symptoms the child will develop.

Prenatal diagnosis can be done through:

chorionic villus sampling (CVS)

typically at 10-12 weeks gestation

amniocentesis (tests the amniotic fluid)

typically at 14-15 weeks gestation

At Boston Children's Hospital, we know how overwhelming a diagnosis of neurofibromatosis can feel, both for your child and for your whole family. Please be assured that your child's doctors will have an ongoing relationship with your child and your family, and that we'll walk through this journey together.

Since a cure for NF has not yet been found, treatment focuses on managing symptoms. This means that we'll customize a treatment plan based on your child's needs, and update it whenever those needs change.

Treatment options might include:

Surgery

If your child has a neurofibroma that's causing her pain or other problems by putting pressure on a nerve or surrounding tissue, depending on its location, it can often be removed. Sometimes parents ask about removing neurofibromas for cosmetic purposes. This can also often be done, but because surgery can leave scars and carries intrinsic risks, and the tumors may grow back, lots of people with NF choose to accept their neurofibromas as part of their condition. This is one of the reasons why it's important that your child be treated by experienced NF specialists who understand when to intervene and when not to intervene.

Medication

Medication can also sometimes be useful in managing your child's symptoms; for example, if she's experiencing headaches or pain caused by tumors pressing on nerves.

Physical therapy

Children with NF1 may have low muscle tone, which could affect coordination and balance. Physical therapy can help by strengthening your child's core muscles.

Supportive devices

If your child has scoliosis or another bone deformity, a supportive device, such as a spinal brace, may help correct the curve.

Individualized Education Plan (IEP)

If your child has delayed development or issues with learning, attention or memory, she may be entitled to an Individualized Education Plan, as mandated by the Individuals with Disabilities Education Act (IDEA). During the creation of an IEP, a team that includes the child's parents, teacher and other specialists works together to create educational goals and a learning plan that takes advantage of the child's strengths and compensates for her weaknesses.

Follow-up

Whether your child has received a diagnosis of NF1 or has yet to meet the diagnosis, the doctors in our Neurofibromatosis Program will see her at least once per year, and arrange more frequent follow-up visits if necessary. Younger children are often seen once every six months. When your child comes to our clinic, we'll:

• examine her skin
• get an update of her medical history
• check her blood pressure
• monitor her height and weight
• do a developmental assessment and/or review her school progress (if she's of school age)
• conduct additional tests as appropriate
• arrange for her to see other Boston Children's specialists if appropriate

If you have any questions about interim follow-up visits, our clinical coordinator will be happy to talk with you.

Coping and support

It's normal and acceptable to go through a range of emotions when your child is waiting for or has received a diagnosis of NF1. Remember that there's lots of help out there – here at Boston Children's, online and out in the community. Some sources of support include:

Parent to parent: Want to talk with someone whose child has been diagnosed with NF1? We can often put you in touch with other families who have been through similar experiences and can share their experience.

Faith-based support: If you are in need of spiritual support, we will help connect you with the Department of Spiritual Care (chaplaincy). Our program includes nearly a dozen clergy representing the Episcopal, Jewish, Lutheran, Muslim, Roman Catholic, Unitarian, and United Church of Christ traditions who will listen to you, pray with you, and help you observe your own faith practices during your hospital experience.

Social work and mental health professionals: Our social workers and mental health clinicians have helped many other families in your situation. We can offer counseling and assistance with issues such as coping with your child's diagnosis, stresses relating to coping with illness and dealing with financial difficulties.

On our patient resources pages, you can read all you need to know about:

• getting to Boston Children's
• accommodations
• navigating the hospital experience
• resources that are available for your family

Some other things you may want to consider:

• Get involved: Consider joining Neurofibromatosis Inc.'s active online support community, finding a way to take part in Children's Tumor Foundation's annual NF Walk or joining a local support group (Neurofibromatosis Inc. offers a good place to start). And your child can meet – and have fun with – other kids with NF at special summer camps, including Camp New Friends offered through Neurofibromatosis Inc or the Children's Tumor Foundation's NF Summer Camp.
• Take care of other relationships: While you may feel like all your energy is focused on your child with NF1, be sure to take care of your other family relationships. Communicate with each other but remember that people deal with emotions differently. Allow each other some leeway in how you communicate. Make sure your child's siblings understand his condition, and reassure them with your attention.
• Maintain a sense of normalcy: Although your regular routine may become centered around your child with NF1, try to keep your life as normal as possible. Continue doing activities that were important to you. Maintaining some sense of normalcy will help your family be in the best mindset to help your child.
• Keep a journal: Keeping a journal of your child's health and medical care can be helpful for both you and your child's medical team, especially if you ever need to change specialists. You can also record your emotions and look back to reflect on how you have managed each phase of the situation.
• Research and learn: Learn everything you can about your child's condition and the treatments available. Read inspirational stories about parents and children who have been through similar situations.

At Boston Children’s Hospital, we’re known for our science-driven approach and our intense culture of innovation—a philosophy that lets us push the boundaries of pediatric care.

We’re one of nine sites selected country-wide for expertise in taking care of patients with neurofibromatosis to participate in the Department of Defense-funded Clinical Trials Consortium. As part of the Consortium, we run trials aimed at finding new ways to treat:

• progressive plexiform neurofibromas
• pediatric brain tumors
• pediatric learning disabilities
• malignant peripheral nerve sheath tumors

We also lead and participate in clinical studies that investigate:

• growth abnormalities in children with NF1, including premature puberty
• bone density in neurofibromatosis
• the relationship between a mutation and the symptoms that people with that mutation may or may not develop
• early ways to detect complications of NF1
• how new blood vessels are created in tumors associated with NF1

If you’d like to find out more about our research and clinical trials or see whether your child might be a candidate, please talk to your child’s doctor or email us at nf@childrens.harvard.edu.