A N I N T R O D U C T I O N F O R PAT I E N T SA N D PA R E N T SJames H. Tonsgard, MD

UnderstandingNeurofibromatosis

3rd Edition

Dedicated to Peter CooperWhose undaunted courage, resolutedetermination, and great kindness

continue to inspire so many.

Neurofibromatosis ProgramThe University of Chicago Hospitals and Clinics

Publication of this booklet was supported by:

Neurofibromatosis Midwestand The University of Chicago

UnderstandingNeurofibromatosis:AN INTRODUCTION FOR PATIENTS AND PARENTS

JAMES H. TONSGARD, M.D., DirectorNeurofibromatosis Program

The University of Chicago Hospitals and Clinics

Photos on pages 1, 7, 15, 21 provided byRick Guidotti at Positive Exposure

Where To Begin?his information is for

families who have recent-

ly been told that one

member may have

Neurofibromatosis (NF). When you

were first told about NF, you may

only have heard the word

Neurofibromatosis and nothing else.

As some of the initial shock wears off,

you will want to know more about

this disorder or group of disorders

because NF really is more than a sin-

gle disorder. This booklet will explain

what NF is, what causes NF, what

your family will need to do about it,

and who can help you.

What Is NF?Neurofibromatosis (NF) is a genetic

disorder that causes growths or

tumors to form on nerves. These can

occur anywhere in the body. NF is

one of the most common genetic dis-

orders. It occurs in every racial and

ethnic group and affects both sexes

equally. There are at least 100,000

people with NF in the United States.

One in every 3,000 babies born has

NF. Even though NF is relatively

common, not many people have

heard of it.

UnderstandingNeurofibromatosisAN INTRODUCTION FOR PATIENTS AND PARENTS

T

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Brandon has NF1. He loves playing basketballand softball and just sports in general. Brandonalso enjoys video games and spending time with

his friends.

NF is one of the most common geneticdisorders. It occurs in both sexes and every

racial and ethnic group.

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Our cells have 46 chromosomes. 23 come from the father and 23 from the

mother, so there are 23 chromosomal pairs. There first 22 are numbered

1 to 22. The last pair are our sex chromosomes.

Each chromosome is made up of genes. A defect or mutation of

the NF gene on chromosome #17 causes NF1. A defect

on a gene within chromosome #22 causes

NF2. Approximately half the people with

NF1 or NF2 inherited the defective

gene from one of their par-

ents. The other half has no

history of the disorder. The

gene became defective very

early in life during the develop-

ment of the embryo.

Note: Since NF1 and NF2 are on different chromosomes they are different though similar

disorders. For this reason it is highly unlikely to have both NF1 and NF2.

Cell

Nucleus

Chromosomes

What Causes NF?Neurofibromatosis (NF) is actuallythe name for at least two or three sep-arate genetic disorders that can affectthe nervous system as well as a num-ber of other parts of the body. Agenetic disorder is caused by anabnormal gene in your body. NF isnot contagious.

That means you can’t catch it fromother people. However, a parent withNF may pass on the disorder tohis/her children.

It is important to understand the twoways children are born with NF: (1)You can inherit an abnormal gene thatcauses NF from one of your parents,or (2) something can go wrong in oneof your genes before birth. This sec-ond way of getting NF is called spon-taneous gene mutation. If you havespontaneous gene mutation, you didnot inherit NF, but you can pass it onto your children.

NF1 and NF2 are separate disordersbecause two different genes are affect-ed. NF1 is caused by a change in agene on chromosome 17. NF2 iscaused by a change in a gene on chro-mosome 22. Because NF1 and NF2are caused by changes in differentgenes, NF1 andNF2 very rarely occurin the same family.

Schwannomatosis appears to be dueto changes in chromosome 22 andshares some features of NF2.

Genetic: inherited or basic, related toinformation contained on genes

There are six major concepts that willhelp you understand how the two kindsof NF are caused and how NF is passedon from parents to children:

1. Genes are inherited material in a cellthat determine how the cell func-tions.

2. NF is caused by an abnormal gene.

3. NF can be due to a spontaneouschange in a gene, or a person mayinherit an abnormal gene.

4. If one of the parents has NF, there isa 50% chance that with each preg-nancy the child will also have NF.

5. NF1 and NF2 are separate disor-ders resulting from changes in differ-ent genes. You usually cannot haveboth NF1 and NF2.

6. A third disorder, Schwannomatosishas some overlap with NF2.

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Autosomal Dominant InheritanceThe NF gene is a dominant gene. Anyone with the gene has the disorder.

Each child always receives a normal copy of the gene from the unaffected

parent and either a normal or faulty gene from the affected parent.

Affected Father(mutated gene)

Unaffected Mother

Affected Son(mutated gene)

Affected Daughter(mutated gene)

UnaffectedDaughter

UnaffectedSon

If you have NF, you have a 50% chance of passing NF on to anychild you have.

About NF1The most common form ofNeurofibromatosis (NF) is NF1,sometimes referred to as vonRecklinghausen’s disease. People withNF1 generally have brown oval or cir-cular spots on the skin called café-au-lait spots and freckles under the arm orin the groin area. Benign soft tumorsor lumps in or under the skin calledneurofibromas and brownish-red spotsin the iris, (the colored part of theeye), called Lisch nodules are present inmost people.

NF1 frequently causes learning diffi-culties. It may affect physical growthand coordination. Tumors may formalong nerves anywhere in the body.

Some signs of NF1 are usually visiblewithin the first year of life.

Other signs of NF1 may develop aspeople get older. For example,

Lisch nodules of the iris develop inteenagers and adults. Neurofibromasfrequently appear or grow duringteenage and adult years. While prob-lems caused by NF1 can be serious,NF1 usually does not keep peoplewho have it from living productivelives.

Some people with NF1 will only havecafé-au-lait spots and neurofibromas,but others may have more difficultproblems. At the present time, it isimpossible to predict what kinds ofproblems an individual will have. Notwo people will be affected exactly thesame way, even within the same fami-ly. However, as we learn more aboutthe different gene changes that causeNF, we may be able to use gene test-ing to help us understand what prob-lems patients may have.

Cafe’-au-lait spots: brown oval spots onthe skin the color of coffee with milk

Benign: not malignant or not cancer

Neurofibroma: Soft tumor in orunder the skin

Lisch nodules: spots on the iris, thecolored part of the eye. These donot interfere with vision

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NF1 can cause cafe’-au-lait spots, benigntumors of the skin, or tumors below the skinaffecting internal organs. Some people willhave only mild problems while other people

will be more severely affected. NF1affects people differently, even within

the same family.

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This is Bev with her son, Eli. Bev andEli have had some difficulties because of their NF,but they maintain a wonderfully cheerful and

positive attitude towards life.

Specific Effects of NF1While NF1 can affect almost anyorgan in the body, many people haveonly a few difficulties.

People with NF1 usually have normalintelligence, but as many as 60 per-cent of children have short attentionspan, hyperactivity, or learning dis-abilities. Problems with visual percep-tion are common and may makespelling and math difficult. Otherchildren can struggle with soundingout words, making it harder for themto learn to read. Problems with organ-ization, impulse control and socializa-tion are frequent. Children with theseproblems can be helped to be success-ful in school. Headaches and hearingissues are also common andmay affectschoolwork.

NF1 frequently affects growth. Peoplemay be shorter or have slightly largerheads than average. NF1 may alsoaffect the growth of bones. Some willhave shrinkage of bone called atrophy,bending or fracture of a long bonethat won’t heal called pseudarthrosis, orcurvature of the spine called scoliosis.

NF1 also causes tumors to form indifferent parts of the body. Smalltumors on or below the surface of theskin, called neurofibromas, are presentin most people.

Some people have tumors or growthsthat involve the skin and deeper tis-sues, including the nerves, called plex-iform neurofibromas. These growthscan sometimes be large and changethe normal shape of a part of the bodyor can affect internal organs.Occasionally, cancer can form in aplexiform neurofibroma.

NF1 may also affect the brain. Brightspots are frequently seen on brain scansin young children. The nerves to theeye may be abnormally large, calledoptic glioma. In a small number ofpeople, NF1 causes brain tumors.

Having NF1 means that there will bechanges in your body that nobody canpredict. Because doctors cannot tell inadvance what will happen to each per-son, and many of the problems arerare, it is important for you to learn allthat you can about NF1.

Atrophy: shrinking or decrease in size

Pseudarthrosis: fracture of a long bone thatwon’t heal

Scoliosis: curvature of the spine

Plexiform neurofibroma: diffuse tumorof the skin or deeper tissues

Bright Spots: spots found on MR scansthat aren’t brain tumors

Optic glioma: a growth on thenerve to the eye

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Matt has NF2. He is a father, husband andmarathon runner. Even with major medical

hurdles he has completed an Ironman competition.

or tumors within the spinal cord(ependymomas) occur in many people.These problems are serious becausethey can cause weakness or seizures,however, the tumors are benign.

While the problems in NF2 can befrightening, there have been impor-tant advances in treatment, detection,and understanding that offer consid-erable hope.

About Other Forms of NFIncluding Schwannomatosis

There are people who do not fit easilyinto a NF1 or NF2 category, or peo-ple in whom the signs of NF are locat-ed on only one side of the body.Additionally, people may have multi-ple tumors along nerves calledschwannomas and pain without anyother problems. These patients have aform of NF called Schwannomatosis.There is some overlap between NF2and Schwannomatosis. Genetic test-ing can be helpful in identifying theseuncommon forms of NF.

Vestibular, acoustic: the nerves for balanceand hearing

Schwannomas, meningiomas: benigntumors of the nerves or brain

Benign: not malignant, not cancer

Cataract: A clouding of the eye lens thatblocks light rays from entering the eye

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NF2 is a completely separate genetic disorderfrom NF1. NF2 causes tumors on the nervesfor hearing and balance. NF2 is very differentfrom NF1 both in its effects on the body and

when it first appears.

About NF2NF2 is sometimes referred to as bilat-eral acoustic neuroma diease. Becauseit affects nerves next to the brain orspinal cord, the problems of NF2 cancause serious disabilities. Even so,many people with NF2 can lead rela-tively normal, rewarding lives andlearn to compensate for deficits theymay have.

In some, signs of NF2 are detectablein childhood, but for themajority, it isnot apparent until late teenage oradult years. People with NF2 mayonly have a few café-au-lait spots onthe skin. Skin tumors are few in num-ber and can be easily overlooked.However, everyone with NF2 hastumors affecting hearing and balance(vestibular schwannomas, previouslycalled acoustic neuromas).

Cataracts in the lens or changes in theretina of the eye are present in mostpeople.Tumors that push on the brainor spinal cord (meningiomas andschwannomas), tumors along theperipheral nerves (schwannomas),

physical exam by a doctor who isfamiliar with NF.

Knowledge of NF is the best tool youand your doctors have in treating thedisorder. A good first step is makingsure you understand how a diagnosisof NF1 or NF2 is made. TheNational Institute of Health offersthe following guidelines (see below).

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How Do I Know that Ior My Child HasNeurofibromatosis?When someone is told that they ortheir child may have NF, one of thefirst questions is: How can you besure? How do I know I have NF?

There is a blood test for NF1 andNF2. MRI’s are also essential forthe diagnosis of NF2.

The diagnosis of NF is usually madeclinically on the basis of a careful

Clinical Diagnostic Features of NF2

Signs of NF2 are not usually present until the teenage years orolder. A person with NF2 should have:

1. Tumors of the vestibular nerve on both sides of the head

OR

2. A single vestibular nerve tumor before age 30 and a mother, father, brother,or sister with NF2

OR

3. A single vestibular schwannoma before age 30 and 2 of the following:neurofibroma, meningioma, ependymoma, schwannoma, or juvenile cataract

OR

4.Multiple meningiomas plus a single vestibular schwannoma or two of thefollowing: schwannoma, ependymoma, neurofibroma, juvenile cataract.

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Clinical Diagnostic Features of NF1

Children may have only a few signs of NF1, and develop otherproblems when they are older. A person with NF1 should exhibit atleast two of the following features:

1. Six or more brown oval or circular spots on the skin called café-au-lait spots

2. Two or more benign skin tumors called neurofibromas, or one diffuse tumor ofthe soft tissue or nerves called a plexiform neurofibroma

3. Freckles under the arm or in the groin region

4. A tumor of the nerve to the eye called an optic glioma

5. Two or more spots on the iris called Lisch nodules

6. A problem of one of the bones such as bowing of a leg with or without a fracture

7. A parent, brother, sister, or child with NF1

Children with NF can have some problemslearning but they can do well, either withthe help of medication and/or educational

programs directed to their needs.

After Neurofibromatosis Diagnosis:Learn About NFBecause many of the problems associ-ated with NF are rare, even amongpeople with NF, most doctors will nothave had enough experience with NFto detect or successfully treat eachsymptom. Successful treatment oftendepends on having a collaborativerelationship between your local physi-cian and other physicians in NF pro-grams at major medical centers.

The best treatment also depends onyour learning about NF so you canunderstand what problems you mayexpect and bring them to the atten-tion of your doctors. If you noticechanges, call your doctor and askwhether the change is associated withNF. It is often much easier to treat theNF related problems that occur if theyare detected early.

What Do You Need to Do?Identification of the genes for NF1and NF2, offers tremendous hope forthe future. For instance, identifyingthe NF1 gene has helped us under-stand how tumors in NF1 form. Aswe understand more about the gene,we hope to predict and control theproblems caused by the abnormalgene.

While there is currently no cure forNF, there are many things you can dothat will make a significant differencein your life or the lives of your chil-dren.

Remember, if your child has NF, youare your child’s protector. If you,yourself, are affected, you must beyour own advocate as well. Thismeans that you must be sure you talkto your doctor about any new prob-lems or concerns.

There are also many professionalsbesides your doctor you can rely onfor help with NF. They include mem-bers of your local NF support group,genetic counselors, teachers, and psy-chologists.

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Talk to your doctor about your problemsand concerns.Write questions down.

Make sure your doctor answersthem and that you

understand the answers.

Working with Your DoctorsIt is important to get the advice of a

doctor who treats many patients with

NF. Don’t hesitate to ask your doctor

about his or her experience with NF.

Do not be afraid to ask for a second

opinion. Your family doctor should be

willing to call an NF clinic to ask for

advice. You may also want to consult

an NF clinic in a medical center on

your own for advice. Doctors at an

NF clinic can then work with your

family doctor to provide you with the

best care.

Once NF has been diagnosed, it is

important to begin a careful, organ-

ized program to spot any changes that

may be due to NF and to keep good

records about these changes. Ask doc-tors for a copy of the examinationreport to keep for your own records.You may also want to keep copies ofyour x-rays or scans so you can discussthem with different doctors. Makeregular doctor visits part of your rou-tine.

Evaluate Your FamilyIt is important to know whether otherpeople in your immediate family haveNF. Identifying who in a family isaffected may be a sensitive and diffi-cult issue since guilt or shame areoften associated with having a geneticdisorder. However, there are good rea-sons for knowing who has NF. Forexample, if you have NF, then any ofyour children can have NF. However,if your child has NF and you are surethat neither of the parents is affected,then the chance of having anotherchild with NF is very small.

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Talk about your concerns with yourfriends and family orother people with NF.

1. Be aware of any changes that may be due to NF.

2. Make regular doctor visits.

3. Keep good medical records.

4. Be cautious about information on the internetabout NF. Many of the complications are quiterare. In addition, complications of NF1 are agespecific. Neither the timing of complications ortheir frequency is explained on the internet.

Knowledge of NF is the best tool you and your doctorshave in treating it. You must learn about NF and howit can affect you. Many of the problems are rare, so you

will need the advice of a doctor who sees manypatients with NF.

You can find support through NF groups like theNF Network. There are many opportunitues to gettogether and and learn from other NF families or

to raise awareness and funds for the cause.

A careful physical examination, is thebest way to determine if someone hasNF, although blood tests for NF1,NF2 and Schwannomatosis can bevery helpful. Sometimes it is also nec-essary to do genetic testing on tumorsamples to evaluate NF2 orSchwannomatosis. You can use thisinformation to plan a family. You maywant to discuss this with your doctoror a genetic counselor. Genetic coun-selors are trained to provide peoplewith information about genetic disor-ders, family planning, and risk of pass-ing on a disorder.

Talk About Your ConcernsDon’t be afraid to talk about NF inyour family. Youmay also want to talkto your friends about your concerns.Be prepared for the possibility thatyour friends or family may not be asunderstanding or as supportive as youmight hope. They may not be readyto talk or want to believe there is aproblem.Theymay not knowwhat tosay. Some family members may feelguilty or angry about having a geneticdisorder.

Unfortunately, there are somesituations where you will need to becautious about discussing NF.

Employers may discriminate against

people with NF, even against parents

of children withNF, because of poten-

tially higher health insurance costs.

Schools may be unsure how to treat a

child with NF unless they are given

specific instructions. Offer informa-

tion about NF to people as it seems

necessary. You also need to be careful

not to overemphasize NF so that

affected family members do not feel

different from the rest of the family.

Remember, the majority of the people

with NF are not sick or handicapped,

and can lead normal, functional lives.

It is important to accept that you or

your child has NF and it may take

time. Many other families have gone

through similar problems. Local NF

groups can be a source of tremendous

support and advice. There are NF

support groups in many states. These

organizations were formed by parents

and individuals with NF to provide

support, advice, and information on

dealing with many aspects of NF.

They are important patient advocates.

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What to Do if You orYour Child Has NF1People with NF1 will need regularphysical exams to check vision, bloodpressure, and spine to evaluate anynew problems or changes. Suddenchanges in the size of a neurofibroma,pain, weakness, or headaches shouldbe brought to your doctor’s immedi-ate attention.

In young children, attention shouldbe given to growth, hearing, vision,speech development, long bones, andspine. Parents should ask teachers iftheir child is having trouble withschoolwork, and whether a learningevaluation is needed. Early detectionand treatment of learning problems iscritical.

In older children and young adults,plexiform neurofibromas need to bechecked and MRIs may be appropri-ate. Time needs to be set aside to talkabout self-esteem and relationshipswith friends.

Young adults as well as teenagersshould understand they can pass NFon to their children.

Scans of the brain, eyes, and spine canbe helpful in NF1 if patients havesymptoms that suggest problems inthose areas.

Because NF1 causes spots as well assmall tumors on the skin that are visi-ble, people with NF1 may have to bebraver than other people. Childrenwith NF are sometimes isolated,rejected, or teased. If this occurs, thebest thing to do is to talk about NFwith your family, the child’s friendsand teachers.

If you are a parent of a child with NF,you should realize that your child maybe frightened or angry about changesin his or her body. It is not helpful foryou to pretend there is no problem.Simple, truthful, and positive expla-nations are reassuring to children suchas “You have a problem that causesspots and some bumps on your skin.You need to see a doctor regularly tomake sure everything is OK.” Youshould talk in more detail withteenagers and make sure they are deal-ing emotionally with their disorder.They can tell their friends that thecafé-au-lait spots and bumps are notcontagious.

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NF1 can cause difficulty with learning. Themost common problems are short attentionspan, difficulty with visual perception,

spelling, and arithmetic.Teens with NF may benefit with others with NF.

What to Do if You orYour Child Has NF2People with NF2 need regular physi-

cal examinations to check their hear-

ing and neurologic function. Genetic

testing is helpful in identifying milder

cases, as well as genetic testing of

tumor samples. Hearing tests and

MRIs of the brain and spinal cord,

and eye exams will probably be need-

ed annually. Because NF2 can ulti-

mately affect hearing in both ears, you

will need to be open to several meth-

ods of communication. Sign lan-

guage, lip reading and assistive tech-

nology offer many opportunities for

the hearing impaired.

People withNF2may needmore than

one complicated surgery. Because

some surgery can lead to permanent

disabilities such as loss of hearing,

timing needs to be carefully consid-

ered. Surgery should be performed

only by a neurosurgical or ear, nose,

and throat team with special expertise

in NF2.

The surgery itself can lead to compli-cations in less experienced hands.Specially trained therapists, audiolo-gists, ophthalmologists, and coun-selors are also essential in the rehabili-tation process. In some instances, sur-gery should be delayed becausetumors show very little growth overmany years and can be watched care-fully.

People with NF2 need to be cautiousof non-standard treatments. Treat-ment of NF2 should always be dis-cussed with physicians who treatmany patients withNF2.While prob-lems in NF2 can be frightening, thereis evidence of significant improve-ments in treatment methods that arevery encouraging and indicate realhope for patients to lead extremelyfunctional lives. There is also a com-munity of people who can provideadvice and support.

Schwannomatosis is a rare conditionthat overlaps with NF2. Genetic test-ing can be helpful in patients withSchwannomatosis and may requiretesting tumor samples.

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Guidelines for Childrenand Adults with NF1Ages 1-5 years1 Consult a doctor with knowledgeof NF1.

2. Check long bones for bowing orfracture.

3. Watch developmental milestonesand performance before preschool.

4. Have an eye exam annually.

5. Check blood pressure.

6. Assess other family members forevidence of NF.

7. Consider genetic testing for theNF1 gene.

Ages 6-14 years1. Watch school performance.

2. Consider tests for learning disabilitiesor hyperactivity.

3. Check back for curvature.

4. Have an eye exam annually to age 10.

5. Have a hearing test.

6. Monitor height, weight, and sexualdevelopment.

7. Monitor changes in or appearanceof neurofibroma.

8. Discuss self-esteem and relationshipswith friends and classmates.

9. Set aside time to talk about NF andhow to respond to questions byfriends.

Ages 15-20 years1. Monitor changes in or appearanceof neurofibroma.

2. Continue to talk about NF,relationships with friends, andself-esteem.

3. Discuss inheritance of NF and thelikelihood of having a child with NF.

Adults1. Watch for changes in tumors as thesecould be signs of cancer.

2. Watch for headaches, weakness, pain,or changes in sensation.

3. Check blood pressure.

Guidelines for Peoplewith NF21. Consult a doctor with knowledge

of NF2.

2. Consider genetic testing for NF2.

3. Have MRI of brain and entire spinalcord annually.

4. Have annual hearing tests.

5. Have careful neurologic examannually.

6. Have eye exam for cataracts andretinal abnormalities.

7. Learn signing or alternative formsof communication.

8. Evaluate other family members forvestibular tumors.

9. Discuss inheritance of NF2.

10.Discuss potential impact of NF2 oncareer and family.

11.Assess resources and support neededfor daily living.

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To find more information, an NF doctoror a local NF Network affiliate,visit us at www.nfnetwork.org

or call 630-510-1115.