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Neurofibromatosis type 1

Reviewed March 2007

What is neurofibromatosis type 1?

Neurofibromatosis type 1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.

Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.

Most adults with neurofibromatosis type 1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia).

During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.

Additional signs and symptoms of neurofibromatosis type 1 include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis). Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention deficit hyperactivity disorder (ADHD) occur frequently in affected individuals.

How common is neurofibromatosis type 1?

Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people worldwide.

What genes are related to neurofibromatosis type 1?

Mutations in the NF1 gene cause neurofibromatosis type 1.

The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many cells, including nerve cells and specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a nonfunctional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. It is unclear how mutations in the NF1 gene lead to the other features of neurofibromatosis type 1, such as café-au-lait spots and learning disabilities.

How do people inherit neurofibromatosis type 1?

Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF1 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new mutations in the NF1 gene and occur in people with no history of the disorder in their family.

Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person's lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.

Where can I find information about treatment for neurofibromatosis type 1?

You may find information on treatment or management of neurofibromatosis type 1 or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about neurofibromatosis type 1?

You may find the following resources about neurofibromatosis type 1 helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Neurofibromatosis-1 (http://www.nlm.nih.gov/medlineplus/ency/article/000847.htm)
    • Health Topic: Neurofibromatosis (http://www.nlm.nih.gov/medlineplus/neurofibromatosis.html)
  • Additional NIH Resources - National Institutes of Health
    • National Human Genome Research Institute (http://www.genome.gov/14514225)
    • National Institute of Neurologic Disorders and Stroke (http://www.ninds.nih.gov/disorders/neurofibromatosis/neurofibromatosis.htm)
  • Educational resources - Information pages
    • Ask the Geneticist: About neurofibromatosis 1 (http://www.askthegen.org/question.php?question_id=33)
    • California Department of Developmental Services (http://www.ddhealthinfo.org/coursebuilder/?id=30)
    • Centre for Genetics Education (http://www.genetics.com.au/pdf/factsheets/fs37.pdf)
    • Children's Hospital Boston (http://www.childrenshospital.org/az/Site1346/mainpageS1346P0.html)
    • Cleveland Clinic Health Information Center (http://www.clevelandclinic.org/health/health-info/docs/3600/3699.asp?index=12103)
    • Genetic Science Learning Center, University of Utah (http://learn.genetics.utah.edu/content/disorders/whataregd/nf1/index.html)
    • Harvard Medical School Center for Neurofibromatosis and Allied Disorders (http://interactive.wgbh.org/nf1-dev/site/)
    • JAMA Patient Page (http://jama.ama-assn.org/cgi/content/full/300/3/352)
    • KidsHealth from the Nemours Foundation (http://kidshealth.org/parent/medical/brain/nf.html)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,275/)
    • Mayo Clinic (http://www.mayoclinic.org/neurofibromatosis/)
    • New York Online Access to Health (http://www.noah-health.org/en/bns/disorders/neuro/)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=636)
    • Penn State Children's Hospital (http://www.hmc.psu.edu/childrens/healthinfo/n/neurofibro.htm)
    • The Merck Manual of Medical Information, Second Home Edition (http://www.merck.com/mmhe/sec06/ch088/ch088d.html)
  • Patient support - For patients and families
    • Children's Tumor Foundation (formerly the National Neurofibromatosis Foundation) (http://www.ctf.org)
    • Family Village (http://www.familyvillage.wisc.edu/lib_neuf.htm)
    • March of Dimes (http://www.marchofdimes.com/pnhec/4439_1217.asp)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Neurofibromatosis+Type+1+(NF-1))
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/neurofib.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=nf1)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=2125)
  • Genetic Tools - Teaching cases (http://www.genetests.org/servlet/access?fcn=y&filename=/tools/cases/nf-40/)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22neurofibromatosis+type+1%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Neurofibromatosis+1[MAJR])+AND+((neurofibromatosis[TI])+AND+(1+OR+I[TI]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=180+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Neurofibromatosis 1 (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=39)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=162200)

What other names do people use for neurofibromatosis type 1?

  • Neurofibromatosis 1
  • NF1
  • Peripheral Neurofibromatosis
  • Recklinghausen Disease, Nerve
  • von Recklinghausen Disease

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about neurofibromatosis type 1?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding neurofibromatosis type 1?

ADHD ; astrocytoma ; attention deficit hyperactivity disorder ; autosomal ; autosomal dominant ; benign ; cancer ; cell ; gene ; glioma ; groin ; hyperactivity ; hypertension ; inguinal ; inheritance ; learning disability ; leukemia ; macrocephaly ; mutation ; nerve cell ; new mutation ; oligodendrocytes ; optic nerve ; pattern of inheritance ; peripheral ; peripheral nerves ; pigmentation ; protein ; Schwann cells ; scoliosis ; short stature ; sign ; stature ; symptom ; tissue ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Arun D, Gutmann DH. Recent advances in neurofibromatosis type 1. Curr Opin Neurol. 2004 Apr;17(2):101-5. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15021234)
  • Baralle D, Mattocks C, Kalidas K, Elmslie F, Whittaker J, Lees M, Ragge N, Patton MA, Winter RM, ffrench-Constant C. Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS). Am J Med Genet A. 2003 May 15;119(1):1-8. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12707950)
  • Cohen, M Michael((Meyer Michael),); Neri, Giovanni; Weksberg, Rosanna; Overgrowth syndromes; New York : Oxford University Press, 2002. p130-151.
  • De Luca A, Bottillo I, Sarkozy A, Carta C, Neri C, Bellacchio E, Schirinzi A, Conti E, Zampino G, Battaglia A, Majore S, Rinaldi MM, Carella M, Marino B, Pizzuti A, Digilio MC, Tartaglia M, Dallapiccola B. NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome. Am J Hum Genet. 2005 Dec;77(6):1092-101. Epub 2005 Oct 26. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16380919)
  • GeneReviews (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=nf1)
  • Hart L. Primary care for patients with neurofibromatosis 1. Nurse Pract. 2005 Jun;30(6):38-43. Review. No abstract available. Erratum in: Nurse Pract. 2005 Jul;30(7):4. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15944472)
  • Huffmeier U, Zenker M, Hoyer J, Fahsold R, Rauch A. A variable combination of features of Noonan syndrome and neurofibromatosis type I are caused by mutations in the NF1 gene. Am J Med Genet A. 2006 Dec 15;140(24):2749-56. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17103458)
  • Kandt RS. Tuberous sclerosis complex and neurofibromatosis type 1: the two most common neurocutaneous diseases. Neurol Clin. 2003 Nov;21(4):983-1004. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14743661)
  • Levine TM, Materek A, Abel J, O'Donnell M, Cutting LE. Cognitive profile of neurofibromatosis type 1. Semin Pediatr Neurol. 2006 Mar;13(1):8-20. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16818171)
  • Reynolds RM, Browning GG, Nawroz I, Campbell IW. Von Recklinghausen's neurofibromatosis: neurofibromatosis type 1. Lancet. 2003 May 3;361(9368):1552-4. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12737880)
  • Rose VM. Neurocutaneous syndromes. Mo Med. 2004 Mar-Apr;101(2):112-6. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15119108)
  • Theos A, Korf BR; American College of Physicians; American Physiological Society. Pathophysiology of neurofibromatosis type 1. Ann Intern Med. 2006 Jun 6;144(11):842-9. Review. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16754926)
  • Tonsgard JH. Clinical manifestations and management of neurofibromatosis type 1. Semin Pediatr Neurol. 2006 Mar;13(1):2-7. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16818170)
  • Ward BA, Gutmann DH. Neurofibromatosis 1: from lab bench to clinic. Pediatr Neurol. 2005 Apr;32(4):221-8. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15797177)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2007
Published: January 23, 2009