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Disease Profile

Neurofibromatosis type 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Infancy

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ICD-10

Q85.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NF1; Type 1 neurofibromatosis; Recklinghausen's disease;

Categories

Musculoskeletal Diseases; Nervous System Diseases

Summary

Neurofibromatosis type 1 (NF1) is a genetic condition that affects the skin, the skeleton and the part of the nervous system outside the brain and spinal cord peripheral nervous system). The main signs and symptoms of NF1 include dark colored spots on the skin (café-au-lait spots), benign growths along the nerves (neurofibromas), and freckles in the underarm and groin. Other symptoms may include colored spots in the eye (Lisch nodules), curvature of the spine, learning disabilities, and an increased risk for cancer. The number of neurofibromas typically increases over time, and some can get large or turn cancerous and need to be removed. The severity and symptoms can vary greatly from person to person. This condition is caused by genetic changes (DNA variants) in the NF1 gene and is inherited in an autosomal dominant pattern. NF1 is diagnosed based on a clinical examination, the specific signs and symptoms, and genetic testing. Treatment is based on the signs and symptoms present in each person.[1][2][3][4]

Symptoms

The following list includes the most common signs and symptoms in people with neurofibromatosis type 1. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list also does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[1][3][5]

  • Non-cancerous growths along the nerves under the skin (cutaneous neurofibromas)
  • Large growths along nerves that may become cancerous (plexiform neuromas)
  • Dark spots of skin (café au lait spots)
  • Freckling, especially in the underarm and groin
  • Pigment in the colored part of the eye (Lisch nodules)
  • Learning disabilities
  • Seizures
  • Autism spectrum disorder
  • High blood pressure
  • Short stature
  • Large head (macrocephaly)
  • Curvature of the spine (scoliosis)

In many cases, the first symptom of neurofibromatosis type 1 (NF1) is multiple small dark colored birth marks known as café-au-lait spots. As they grow older, people with NF1 develop neurofibromas, benign tumors that can affect nearly any nerve in the body. These tumors usually grow on or just underneath the skin, but neurofibromas can also grow in other places in the body and may even affect multiple nerves. Some of these tumors can cause skin irritation, nerve damage, or affect a person’s appearance. In addition, some of these tumors may become cancerous. The most common type of cancerous tumors in people with NF1 are malignant peripheral nerve sheath tumors.[1] 

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Cause

Neurofibromatosis type 1 is caused by genetic changes (DNA variants) in the NF1 gene.[1]

Diagnosis

The diagnosis of neurofibromatosis type 1 (NF1) is based on clinical examination and the presence of characteristic signs and symptoms. Diagnostic criteria have been published to help health care professionals make a diagnosis of NF1[6]. Genetic testing for genetic changes (DNA variants) in the NF1 gene is available, and can help make the diagnosis or can help exclude other conditions that might look like NF1.[3][4]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    The treatment of neurofibromatosis type 1 (NF1) is based on the signs and symptoms present in each person. Treatment may include surgery to remove neurofibromas that are disfiguring, irritating or cancerous. There is currently no way to prevent or stop the growth of the tumors associated with NF1. Guidelines have been published for taking care of children and adults with NF1.[2][7][8]

    Specialists involved in the care of someone with NF1 may include:[1]

    • Neurologist
    • Neurosurgeon
    • Ophthalmologist
    • Genetics specialist
    • Developmental specialist

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • Selumetinib(Brand name: Koselugo) Manufactured by AstraZeneca Pharmaceuticals
      FDA-approved indication: April 2020, selumetinib (Koselugo) was approved for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).
      National Library of Medicine Drug Information Portal
    Medical Terms Other Names
    Learn More:
    HPO ID
    80%-99% of people have these symptoms
    Astrocytoma
    0009592
    Delayed puberty
    Delayed pubertal development
    Delayed pubertal growth
    Pubertal delay

    [ more ]

    0000823
    Generalized hyperpigmentation
    0007440
    Intellectual disability, mild
    Mental retardation, borderline-mild
    Mild and nonprogressive mental retardation
    Mild mental retardation

    [ more ]

    0001256
    Lisch nodules
    0009737
    Macule
    Flat, discolored area of skin
    0012733
    Melanocytic nevus
    Beauty mark
    0000995
    Meningioma
    0002858
    Multiple cafe-au-lait spots
    0007565
    Multiple lipomas
    Multiple fatty lumps
    0001012
    Plexiform neurofibroma
    0009732
    Specific learning disability
    0001328
    Subcutaneous nodule
    Firm lump under the skin
    Growth of abnormal tissue under the skin

    [ more ]

    0001482
    30%-79% of people have these symptoms
    Ataxia
    0001251
    Attention deficit hyperactivity disorder
    Attention deficit
    Attention deficit disorder
    Attention deficit-hyperactivity disorder
    Attention deficits
    Childhood attention deficit/hyperactivity disorder

    [ more ]

    0007018
    Cryptorchidism
    Undescended testes
    Undescended testis

    [ more ]

    0000028
    Freckling
    0001480
    Genu valgum
    Knock knees
    0002857
    Headache
    Headaches
    0002315
    Hearing impairment
    Deafness
    Hearing defect

    [ more ]

    0000365
    Heterochromia iridis
    Different colored eyes
    0001100
    Memory impairment
    Forgetfulness
    Memory loss
    Memory problems
    Poor memory

    [ more ]

    0002354
    Neurological speech impairment
    Speech disorder
    Speech impairment
    Speech impediment

    [ more ]

    0002167
    Paresthesia
    Pins and needles feeling
    Tingling

    [ more ]

    0003401
    Proptosis
    Bulging eye
    Eyeballs bulging out
    Prominent eyes
    Prominent globes
    Protruding eyes

    [ more ]

    0000520
    Recurrent fractures
    Increased fracture rate
    Increased fractures
    Multiple fractures
    Multiple spontaneous fractures
    Varying degree of multiple fractures

    [ more ]

    0002757
    Skeletal dysplasia
    0002652
    Slender long bone
    Long bones slender
    Thin long bones

    [ more ]

    0003100
    Tall stature
    Increased body height
    0000098
    5%-29% of people have these symptoms
    Abnormal electroretinogram
    0000512
    Abnormal eyelid morphology
    Abnormality of the eyelid
    Abnormality of the eyelids

    [ more ]

    0000492
    Abnormal hair quantity
    0011362
    Abnormality of retinal pigmentation
    0007703
    Abnormality of the hip bone
    Abnormality of the hips
    0003272
    Abnormality of the respiratory system
    0002086
    Abnormality of the upper urinary tract
    0010935
    Arterial stenosis
    Narrowing of an artery
    0100545
    Cataract
    Clouding of the lens of the eye
    Cloudy lens

    [ more ]

    0000518
    Chorioretinal coloboma
    Birth defect that causes a hole in the innermost layer at the back of the eye
    0000567
    Chronic myelogenous leukemia
    0005506
    Corneal opacity
    0007957
    Genu varum
    Outward bow-leggedness
    Outward bowing at knees

    [ more ]

    0002970
    Glaucoma
    0000501
    Hydrocephalus
    Too much cerebrospinal fluid in the brain
    0000238
    Hypertension
    0000822
    Hypopigmented skin patches
    Patchy loss of skin color
    0001053
    Joint stiffness
    Stiff joint
    Stiff joints

    [ more ]

    0001387
    Kyphosis
    Hunched back
    Round back

    [ more ]

    0002808
    Macrocephaly
    Large head circumference
    Large head
    Increased size of skull

    [ more ]

    0000256
    Myopia
    Close sighted
    Near sighted
    Near sightedness
    Nearsightedness

    [ more ]

    0000545
    Neoplasm of the gastrointestinal tract
    Gastrointestinal tract tumor
    GI tract tumor

    [ more ]

    0007378
    Pheochromocytoma
    0002666
    Conditions with similar signs and symptoms from Orphanet
    Legius syndrome (see this term) is often clinically indistinguishable from NF1 and is seen in about 2% of people fulfilling NF1 diagnostic criteria. There are however a small number of individuals with NF1 who like Legius syndrome patients do not develop non-pigmentary manifestations. Constitutional mismatch repair deficiency syndrome should be considered. Other differential diagnoses include McCune-Albright syndrome, Noonan syndrome with lentigines and Proteus syndrome. Most cases of multiple non-ossifying fibromatosis are cases of NF1 (see these terms).
    Visit the Orphanet disease page for more information.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Neurofibromatosis type 1. This website is maintained by the National Library of Medicine.
      • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
      • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Neurofibromatosis type 1. Click on the link to view a sample search on this topic.

          References

          1. Friedman JM. Neurofibromatosis 1. GeneReviews. Updated June 2019; https://www.ncbi.nlm.nih.gov/books/NBK1109/.
          2. Korf BR, Lobbous M, Metrock LK. Neurofibromatosis type 1 (NF1): Management and prognosis. UpToDate. Updated Dec 2, 2019; https://www.uptodate.com/contents/neurofibromatosis-type-1-nf1-management-and-prognosis.
          3. Ly KI, Blakeley JO. The Diagnosis and Management of Neurofibromatosis Type 1. Med Clin North Am. Nov 2019; 103(6):1035-1054. https://pubmed.ncbi.nlm.nih.gov/31582003.
          4. Giugliano T, Santoro C, Torella A, Del Vecchio Blanco F, Grandone A et al. Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders.. Genes (Basel). Jul 31, 2019; 10(8):580. https://pubmed.ncbi.nlm.nih.gov/31370276.
          5. Bruce R Korf, MD, PhD. Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis. UpToDate. June 2015; Accessed 7/19/2015.
          6. National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA July 13-15, 1987. Neurofibromatosis. 1988; 1(3):172-178. https://pubmed.ncbi.nlm.nih.gov/3152465.
          7. Miller DT, Freedenberg D, Schorry E, Ullrich NJ, Viskochil D, Korf BR. AAP COUNCIL ON GENETICS, AAP AMERICAN COLLEGE OF MEDICAL GENETICS AND GENOMICS. Health Supervision for Children With Neurofibromatosis Type 1.. Pediatrics. May 2019; 143(5):e20190660. https://pubmed.ncbi.nlm.nih.gov/31010905.
          8. Stewart DR, Korf BR, Nathanson KL, Stevenson DA, Yohay K. Care of adults with neurofibromatosis type 1: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. Jul 2018; 20(7):671-82. https://pubmed.ncbi.nlm.nih.gov/30006586.

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