Home > Diagnoses & Conditions > Neurofibromatosis Type 1 > Treatment & Management

Neurofibromatosis Type 1 - Treatment & Management

Page Contents

Overview

There is no treatment for the underlying genetic defect that causes neurofibromatosis type 1 (NF1). The treatment of patients with NF1 is based on identifying manifestations of NF1 and treating complications due to these manifestations accordingly.

Primary Care Roles

In addition to well child and acute care evaluations, the Medical Home provider may wish to schedule chronic care visits where problems associated with NF1 may be monitored for if an NF1 specific clinic is not available. These include surveillance of neurofibromas, especially during puberty where accelerated tumor growth may occur, scoliosis, hypertension, and the management of learning disorders.

Pearls And Alerts

Individuals with NF1 are generally shorter than the general population with a larger head (relative macrocephaly). Specific growth charts for individuals with NF1 are available and can prove useful in differentiating NF1-related issues from general pediatric causes of short stature. [Friedman: 1999] [Clementi: 1999]

Practice Guidelines

Hersh JH.
Health supervision for children with neurofibromatosis.
Pediatrics. 2008;121(3):633-42. PubMed abstract / Full Text

Viskochil DH.
Neurofibromatosis Type 1.
Management of Genetic Syndromes, 3rd Edition. 2010; 549-568. New York: Wiley-Blackwell; http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Excellent review of NF1 by an expert in the field. Book is a great resource for Medical Home providers, with chapters on 25 different genetic conditions.

Friedman JM.
Neurofibromatosis 1.
Copyright, University of Washington, Seattle. 1997-2004; (2002) http://www.geneclinics.org/servlet/access?db=geneclinics&site=gt&id=88.... In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Available at http://www.genetests.org/. Accessed on 8/14/04.
A concise and well organized review of NF1 with a focus on gene testing.

Systems

Hematology/Oncology

The cutaneous neurofibromas in neurofibromatosis type 1 (NF1) are benign. Other tumors, however, occur and include but are not limited to optic pathway tumors, leukemia, malignant peripheral nerve sheath tumors, rhabdomyosarcomas, pheochromocytomas, and various brain tumors. The brain tumors sometimes can be managed more conservatively than similar presentations in the general population (they usually have a more indolent course), but malignant peripheral nerve sheath tumors tend to be more aggressive. [Korf: 2000] Treatment of the various tumors in NF1 is an area of ongoing research. If a patient develops unexplained pain and/or rapid tumor growth, one should be suspicious for a neoplasm. Referral to a tertiary care center familiar with NF1 and sarcoma management is recommended for concerns of tumors other than the benign neurofibromas.

The benign dermal neurofibromas generally cause no significant problems. They can be removed for cosmetic reasons, pain, or if they are in an area where the tumor catches onto clothing etc. The mainstay of treatment is surgical excision. [Packer: 2002] Excision does not mean the neurofibroma will not return, as it is difficult to excise the entire tumor. The neurofibromas usually present after the pigmentary lesions and increase with age with a more rapid increase during puberty and pregnancy. Various modalities of surgical excision have been adopted at different centers, but presently there is not an accepted protocol for medical management or prevention.

Subspecialist Collaborations and Other Resources

Pediatric Dermatology (see Services below for relevant providers)

Pediatric dermatologists may be helpful in the management of neurofibromas.

General Pediatric Surgery (see Services below for relevant providers)

Pediatric surgeons may need to be involved in the excision of large neurofibromas, depending on size and location.

Eyes/Vision

Individuals with NF1 should have an ophthalmologic evaluation by an experienced ophthalmologist yearly until late adolesence. The primary care physician should perform a routine eye exam looking for proptosis, strabismus, etc., but the typical findings of NF1 usually can only be seen by an experienced ophthalmologist. Lisch nodules are benign iris hamartomas that aid in the diagnosis of NF1, but have no clinical consequences. Optic pathway tumors often can be picked up by clinical exam by an experienced ophthalmologist (pale optic nerve) and then confirmed by MRI scan. Asymptomatic patients are often followed closely with dedicated sequential brain MRI studies and frequent ophthalmological evaluations. If there is vision loss or increased growth of the tumor as measured by sequential MRI, then medical management is sometimes initiated with low-level chemotherapy. These treatment options are considered, but the tumors may regress or remain stable in NF1 patients. [Listernick: 1999] This is an ongoing area of research, therefore referral to neurooncology is indicated when an optic glioma is identified.

Subspecialist Collaborations and Other Resources

Pediatric Ophthalmology (see Services below for relevant providers)

Pediatric ophthalmologists should follow children with NF1 on at least a yearly basis.

Nutrition/Growth/Bone

The osseous abnormalities classically associated with NF1 include long bone dysplasia, scoliosis, and sphenoid wing dysplasia. Other osseous findings include short stature (compared to familial background), bone cysts, and relative macrocephaly. Of NF1 individuals, approximately 1/3 have one or more orthopedic findings. [Crawford: 1999]

Long bone dysplasia is seen in 5% of NF1 individuals and classically involves the tibia (though involvement of other long bones has been reported), with fibular involvement seen in 43% of those with long bone dysplasia. Tibial pseudarthrosis is strongly associated with NF1; greater than or equal to 50% of individuals with tibial pseudarthrosis have NF1. The bowing usually presents before 4 years of age. The typical presentation is anterior lateral bowing leading to fracture and non-union or pseudarthrosis. Before 2 years of age, 53% of NF1 individuals with long bone bowing will experience a fracture, and fractures have been seen in utero. [Stevenson: 1999]

The extremities (particularly the lower leg) of children with NF1 should be carefully examined for any anterior-lateral bowing. If bowing is evident, an x-ray and referral to orthopedics should be made. Bracing should then be initiated if fractures has not yet occurred. Treatment of pseudarthrosis is controversial and studies are underway to determine the clinical outcome and long-term treatment results of this complication.

Both idiopathic and dystrophic forms of scoliosis are seen in individuals with NF1 (combined 10-33%), with a typical onset between 7-16 years. [Vitale: 2002] The dystrophic form is defined by one of the following dystrophic osseous finding: spinal canal widening, vertebral body narrowing, rib-penciling, vertebral wedging, defective pedicles, and vertebral scalloping. The non-dystrophic form of scoliosis is more common in children with NF1 [Vitale: 2002], but dystrophic scoliosis (typical presenting with a sharply angulated curve) is progressively debilitating and requires a more aggressive approach, with surgical intervention sooner. Every child with NF1 should be screened for scoliosis and any suspicion should prompt a PA and lateral erect thoracolumbar spine image. Referral to orthopedics is indicated if scoliosis is evident.

Sphenoid wing dysplasia is a congenital abnormality seen in approximately 7-11% of NF1 patients. [Friedman: 1997] [Young: 2002] It is unilateral, and approximately 50% will have a clinically apparent plexiform neurofibroma of the temporal-orbital region. One should have a lower index of suspicion for facial plexiforms in individuals with sphenoid wing dysplasia, and they may benefit from earlier imaging by MRI. Exophthalmosis is a rare complication that may require intervention, but the sphenoid wing dysplasia usually does not cause significant clinical complications or require therapeutic management.

Subspecialist Collaborations and Other Resources

Pediatric Orthopedics (see Services below for relevant providers)

Children with NF1 should be evaluated and managed by pediatric orthopedics if not available as part of a multi-disciplinary NF1 specific clinic.

Learning/Education/Schools

Learning disabilities are common in neurofibromatosis (NF1) with educational difficulties being seen in approximately 40-60% of individuals. Additional educational resources will be needed by many individuals with NF1 to help them reach their potential. The school system should be informed of the association of learning disabilities in NF1 with a recommendation for a full evaluation and an individualized program to optimize educational outcomes. Reports have also shown an association between attention deficit hyperactivity disorder (ADHD) and NF1 [Koth: 2000]. Patients should be screened for ADHD and, if positive, appropriately managed. Although clinical trials are currently underway testing targeted pharmacologic agents for ADHD, treatment at this time should be the same as for individuals without NF1. Individuals with a large NF1 gene deletion have been noted to have an increased chance for cognitive/developmental delay [Viskochil: 2010]. A karyotype and FISH study (flourescence in situ hybridization) looking for an NF1 gene deletion should be performed when cognitive impairment is a prominent feature.

Ears/Hearing

Sensorineural hearing loss (5%) is relatively infrequent in neurfibromatosis type 1 (NF1), but primary care physicians should be sensitized to any hearing deficits and refer to audiology when indicated. The exact etiology is not well delineated. [Pensak: 1989]. Every child should have a newborn hearing screen.

Subspecialist Collaborations and Other Resources

Audiology (see Services below for relevant providers)

Hearing evaluations are available through these providers.

Neurology

Recurrent headaches are more common in children with NF1 than in the general population, with approximately 1/3 of those migrainous in nature. [DiMario: 2000] Hypertension should be ruled out in all children with headaches. Because individuals with NF1 are predisposed to brain tumors, including optic gliomas, astrocytomas, and plexiform neurofibromas, it is difficult to decide when it is appropriate to order imaging studies. Children and adolescents with NF1 who present with new headaches or changes in their headaches should probably be imaged, although there is no data to support this. In fact, some investigators recommend that children with NF should be imaged with MRI on a yearly basis, [Mentzel: 2005] although other investigators have found that routine brain MRIs don't change clinical outcome. [Blanchard: 2009] Children and adolescents should receive headache medication as appropriate if there is no underlying cause found. These should include rescue medications and preventative medications if headaches are occurring often and interfering with school/employment function.

Seizures are seen at a slightly increased frequency in individuals with NF1 (5-7%) as compared to the general population. [Young: 2002] The natural history and types of seizures in NF1, however, are similar to that in the general population [Korf: 1993]. The seizures are usually not the result of an anatomic abnormality, but any NF1 individual with seizure activity should have an MRI of the brain to look for structural abnormalities and tumors, and be evaluated by a neurologist.

Cerebral arteriopathy and subsequent risk of stroke [Rea: 2009]are found in approximately 6% of children with NF1, possibly more in those with optic glioma. It has therefore been suggested that MRA be included with MRI when performed for other reasons, such as screening for optic glioma. [Payne: 2010] If cerebral arteriopathy is found, pediatric neurology or neurosurgery should be consulted for the possibility of medical and/or neurosurgical treatment.

Subspecialist Collaborations and Other Resources

Pediatric Neurology (see Services below for relevant providers)

If recurrent headaches and/or seizures occur, pediatric neurology may be helpful.

Cardiology

In NF1, congenital heart disease (2-4%) and hypertension (4%) are infrequent but can be serious complications. The most common associated lesion is valvar pulmonic stenosis. [Lin: 2000] A referral to cardiology and routine echocardiography are not indicated unless the patient has clinical findings.

Vasculopathies have been documented in NF1 and can involve the heart, renal arteries, and brain. [Friedman: 2002] Hypertension should be taken seriously in any individual with NF1 and blood pressure measurements performed at every visit, including four-extremity blood pressures at least once to help rule out coarctation if hypertension is present. Hypertension may be the result of renal artery stenosis, coarctation of the aorta or, less commonly, pheochromocytomas [Xu: 1992]. Most NF1 individuals with hypertension, however, have typical essential hypertension. Given the possibility of other causes, individuals with hypertension should receive imaging studies to rule out renal artery stenosis and be referred to nephrology. If the above evaluation is normal, a work-up for pheochromocytoma should be considered in individuals with hypertension and/or signs of excess catecholamine release.

Subspecialist Collaborations and Other Resources

Pediatric Nephrology (see Services below for relevant providers)

Consider management by pediatric nephrology if hypertension is present.

Pediatric Cardiology (see Services below for relevant providers)

Pediatric cardiology may be helpful if cardiac problems are suspected.

Recreation & Leisure

Some individuals with NF1 have difficulty with coordination, which may impact their involvement in sporting activities. We recommend that they be encouraged to continue with various activities to keep a healthy lifestyle. See Resources below for recreational therapy and camping programs.

Resources

Information & Support

For Professionals

Neurofibromatosis 1 (GeneReviews)
Detailed overview of neurofibromatosis (NF1), testing, genetics, resources, reviews, and research; hosted by NCBI (National Center for Biotechnology Information).

For Parents and Patients

Support

Neurofibromatosis, Inc.
NF, Inc. is a national organization whose mission is to create a community of support for those affected by NF through education, advocacy, coalitions, raising public awareness, and supporting research for treatments and a cure; sponsor a limited number of local groups.

General

Neurofibromatosis type 1 (Genetic Science Learning Center)
From a science and health education program at the University of Utah that provides educational materials and programs; this page focuses on the genetics of NF1.

Neurofibromatosis (MedlinePlus)
From the National Library of Medicine and National Insitutes of Health.

Neurofibromatosis type 1 (Genetics Home Reference)
This site, sponsored by the National Library of Medicine, offers a wealth of information and links to more information about neurofibromatosis type 1. The information is aimed at consumers/patients/families.

Understanding NF1 (Harvard University)
A medical resource about NF1 for parents, patients, and providers from the Harvard Medical School Center for Neurofibromatosis and Allied Disorders; offers several frequently asked questions and their answers.

Practice Guidelines

Friedman JM.
Neurofibromatosis 1.
Copyright, University of Washington, Seattle. 1997-2004; (2002) http://www.geneclinics.org/servlet/access?db=geneclinics&site=gt&id=88.... In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Available at http://www.genetests.org/. Accessed on 8/14/04.
A concise and well organized review of NF1 with a focus on gene testing.

Hersh JH.
Health supervision for children with neurofibromatosis.
Pediatrics. 2008;121(3):633-42. PubMed abstract / Full Text

Viskochil DH.
Neurofibromatosis Type 1.
Management of Genetic Syndromes, 3rd Edition. 2010; 549-568. New York: Wiley-Blackwell; http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Excellent review of NF1 by an expert in the field. Book is a great resource for Medical Home providers, with chapters on 25 different genetic conditions.

Services

Adaptive Recreation

See all Adaptive Recreation services providers (42) in our database.

Audiology

See all Audiology services providers (59) in our database.

Camps

See all Camps services providers (84) in our database.

General Pediatric Surgery

See all General Pediatric Surgery services providers (2) in our database.

Pediatric Cardiology

See all Pediatric Cardiology services providers (1) in our database.

Pediatric Dermatology

See all Pediatric Dermatology services providers (2) in our database.

Pediatric Nephrology

See all Pediatric Nephrology services providers (1) in our database.

Pediatric Neurology

See all Pediatric Neurology services providers (3) in our database.

Pediatric Ophthalmology

See all Pediatric Ophthalmology services providers (4) in our database.

Pediatric Orthopedics

See all Pediatric Orthopedics services providers (2) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for articles on Neurofibromatosis Type 1 in children for the last 3 years

Max JE, Robin DA, Lindgren SD, Smith WL Jr, Sato Y, Mattheis PJ, Stierwalt JA, Castillo CS.
Traumatic brain injury in children and adolescents: psychiatric disorders at one year.
J Neuropsychiatry Clin Neurosci. 1998;10(3):290-7. PubMed abstract

Authors

Author: David Stevenson MD, 11/2004
Contributing Author: Lynne M Kerr MD, PhD, 9/2010
Reviewing Authors: Karin Dent MS, CGC, 11/2004
David Viskochil MD, PhD, 10/2004
Content Last Updated: 7/2010

Page Bibliography

Blanchard G, Pinson S, Rousselle C, Lorthois S, Combemale P, Bernard M, Lion Francois L.
[Usefulness of systematic brain magnetic resonance imaging in children with neurofibromatosis type 1].
(Article in French) Arch Pediatr. 2009;16(12):1527-32. PubMed abstract

Clementi M, Milani S, Mammi I, Boni S, Monciotti C, Tenconi R.
Neurofibromatosis type 1 growth charts.
Am J Med Genet. 1999;87(4):317-323. PubMed abstract
Article reports growth differences in NF1.

Crawford AH, Schorry EK.
Neurofibromatosis in children: the role of the orthopaedist.
J Am Acad Orthop Surg. 1999;7(4):217-230. PubMed abstract
Excellent review of the orthopedic manifestations of NF1 particularly for orthopedic physicians managing NF1 patients.

DiMario FJ Jr, Langshur S.
Headaches in patients with neurofibromatosis-1.
J Child Neurol. 2000;15(4):235-8. PubMed abstract

Friedman JM, Arbiser J, Epstein JA, Gutmann DH, Huot SJ, Lin AE, McManus B, Korf BR.
Cardiovascular disease in neurofibromatosis 1: report of the NF1 Cardiovascular Task Force.
Genet Med. 2002;4(3):105-11. PubMed abstract
Summary of experts on NF1 from a task force meeting on cardiovascular disease in NF1, with recommendations on surveillance and diagnostic evaluation.

Friedman JM, Birch PH.
Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients.
Am J Med Genet. 1997;70(2):138-143. PubMed abstract
A large case series utilizing an international database; authors are international authorities on clinical aspects of NF1. Excellent review, focused on clinical characteristics and natural history.

Friedman JM, Gutmann DH, MacCollin M, Riccardi VM.
Neurofibromatosis: Phenotype, Natural History, and Pathogenesis.
3rd ed. Baltimore, MD: Johns Hopkins University Press; 1999. 080186285X
Excellent overview of NF1 by some of the world experts on NF1.

Korf BR.
Malignancy in neurofibromatosis type 1.
Oncologist. 2000;5(6):477-85. PubMed abstract
Excellent review of the malignancies in NF1 with particular focus on malignant peripheral nerve sheath tumors.

Korf BR, Carrazana E, Holmes GL.
Patterns of seizures observed in association with neurofibromatosis 1.
Epilepsia. 1993;34(4):616-20. PubMed abstract
Retrospective review of 359 NF1 individuals looking at seizure frequency.

Koth CW, Cutting LE, Denckla MB.
The association of neurofibromatosis type 1 and attention deficit hyperactivity disorder.
Neuropsychol Dev Cogn Sect C Child Neuropsychol. 2000;6(3):185-94. PubMed abstract
Study compared the ADHD status of children affected with NF-1 to that of their unaffected-NF-1 siblings and to that of their biological parents suggesting ADHD may occur as a component of NF1.

Lin AE, Birch PH, Korf BR, Tenconi R, Niimura M, Poyhonen M, Armfield Uhas K, Sigorini M, Virdis R, Romano C, Bonioli E, Wolkenstein P, Pivnick EK, Lawrence M, Friedman JM.
Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1.
Am J Med Genet. 2000;95(2):108-17. PubMed abstract
Review of 2322 NF1 individuals from NF1 database documenting cardiovascular abnormalities seen in NF1.

Listernick R, Gutmann DH.
Tumors of the optic pathway.
Neurofibromatosis: Phenotype, Natural History, and Pathogenesis. 1999; 203-230. Baltimore, MD: Johns Hopkins University Press
Section, in book on NF1, reviewing optic pathway tumors by some of the world experts on NF1.

Mentzel HJ, Seidel J, Fitzek C, Eichhorn A, Vogt S, Reichenbach JR, Zintl F, Kaiser WA.
Pediatric brain MRI in neurofibromatosis type I.
Eur Radiol. 2005;15(4):814-22. PubMed abstract

Packer RJ, Rosser T.
Therapy for plexiform neurofibromas in children with neurofibromatosis 1: an overview.
J Child Neurol. 2002;17(8):638-41; discussion 646-51. PubMed abstract

Payne JM, Moharir MD, Webster R, North KN.
Brain structure and function in neurofibromatosis type 1: current concepts and future directions.
J Neurol Neurosurg Psychiatry. 2010;81(3):304-9. PubMed abstract

Pensak ML, Keith RW, Dignan PS, Stowens DW, Towbin RB, Katbamna B.
Neuroaudiologic abnormalities in patients with type 1 neurofibromatosis.
Laryngoscope. 1989;99(7 Pt 1):702-6. PubMed abstract
Study of 44 NF1 indiviudals using ABR.

Rea D, Brandsema JF, Armstrong D, Parkin PC, Deveber G, Macgregor D, Logan WJ, Askalan R.
Cerebral Arteriopathy in Children With Neurofibromatosis Type 1.
Pediatrics. 2009;. PubMed abstract

Stevenson DA, Birch PH, Friedman JM, Viskochil DH, Balestrazzi P, Boni S, Buske A, Korf BR, Niimura M, Pivnick EK, Schorry EK, Short MP, Tenconi R, Tonsgard JH, Carey JC.
Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1.
Am J Med Genet. 1999;84(5):413-419. PubMed abstract
One of the largest case series, through a multi-center, international collaboration, of tibial pseudarthrosis in NF1 describing the natural history and presentation of this hard to treat complication of NF1.

Viskochil DH.
Neurofibromatosis Type 1.
Management of Genetic Syndromes, 3rd Edition. 2010; 549-568. New York: Wiley-Blackwell; http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Excellent review of NF1 by an expert in the field. Book is a great resource for Medical Home providers, with chapters on 25 different genetic conditions.

Vitale MG, Guha A, Skaggs DL.
Orthopaedic manifestations of neurofibromatosis in children: an update.
Clin Orthop. 2002;(401):107-118. PubMed abstract
A recent review of the orthopedic manifestations of NF1. Very well organized and informative.

Xu W, Mulligan LM, Ponder MA, Liu L, Smith BA, Mathew CG, Ponder BA.
Loss of NF1 alleles in phaeochromocytomas from patients with type I neurofibromatosis.
Genes Chromosomes Cancer. 1992;4(4):337-42. PubMed abstract
Study reports the association of pheochromocytomas with NF1.

Young H, Hyman S, North K.
Neurofibromatosis 1: clinical review and exceptions to the rules.
J Child Neurol. 2002;17(8):613-621. PubMed abstract
Concise, up to date, review of clinical aspects of NF1 with focus on unusual manifestations.