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Disease Profile

Neurofibromatosis type 2

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

All ages

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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)

NF2; Neurofibromatosis central type; Acoustic schwannomas bilateral;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

Neurofibromatosis type 2 (NF2) is a disorder characterized by the growth of noncancerous tumors of the nervous system. Childhood symptoms include skin growths and eye findings. Almost all people with NF2 develop vestibular schwannomas affecting both ears by age 30. Other tumors of the central nervous system (the brain and spinal cord), skin and eye are also common. The signs and symptoms vary from person to person. The severity depends on the size, location, and number of tumors. NF2 is caused by changes (mutations) in the NF2 gene and is inherited in an autosomal dominant manner. It is diagnosed based on a clinical examination and the symptoms. Genetic testing may be helpful. The treatment is based on managing the signs and symptoms and may include surgery and medications.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Neurofibromatosis type 2 (NF2). 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 does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[1][2]

  • Benign tumors along the nerves going from the inner ear to the brain (vestibular schwannomas)
    • Ringing in the ear
    • Hearing loss
    • Balance problems
  • Benign tumors of the central nervous system (meningiomas)
    • Muscle weakness or numbness
    • Dizziness
    • Seizures
  • Retinal tumors (hamartomas)
  • Clouding of the lens (cataracts)
  • Skin plaques

Children with NF2 may develop plaque-like lesions of the skin, eye findings including cataracts and retina changes, and nerve damage. By age 30, most individuals with NF2 develop vestibular schwannomas which cause ringing in the ears, dizziness and balance problems. Other symptoms that may develop include central nervous system tumors such as schwannomas and meningiomas. The severity of NF2 depends on the size and number of tumors that occur.[1][2][4]

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.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Neuroma
Nerve tumor
Pinched nerve

[ more ]

0030430
30%-79% of people have these symptoms
Abnormal cerebellum morphology
Abnormality of the cerebellum
Cerebellar abnormalities
Cerebellar abnormality
Cerebellar anomaly

[ more ]

0001317
Abnormal hand morphology
Abnormal shape of hand
0005922
Babinski sign
0003487
Bilateral vestibular Schwannoma
0009589
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Constipation
0002019
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Dysuria
Painful or difficult urination
0100518
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Hyperesthesia
0100963
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Impaired vibratory sensation
Decreased vibration sense
Decreased vibratory sense
Diminished vibratory sense
Impaired vibratory sense

[ more ]

0002495
Intracranial meningioma
0100009
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints

[ more ]

0001382
Motor delay
0001270
Myelopathy
0002196
Overbite
0011094
Peripheral Schwannoma
0009593
Posterior subcapsular cataract
0007787
Sensorineural hearing impairment
0000407
Short stature
Decreased body height
Small stature

[ more ]

0004322
Slurred speech
0001350
Spastic dysarthria
0002464
Spastic paraparesis
0002313
Specific learning disability
0001328
Spinal cord tumor
Tumor of the spinal cord
0010302
Upper limb muscle weakness
Decreased arm strength
Weak arm

[ more ]

0003484
5%-29% of people have these symptoms
Abnormal thumb morphology
Abnormality of the thumb
Abnormality of the thumbs
Thumb deformity

[ more ]

0001172
Abnormality of the nares
Abnormality of the nostrils
0005288
Abnormality of the optic nerve
Optic nerve issue
0000587
Amblyopia
Lazy eye
Wandering eye

[ more ]

0000646
Ankle clonus
Abnormal rhythmic movements of ankle
0011448
Anxiety
Excessive, persistent worry and fear
0000739
Blindness
0000618
Brain stem compression
0002512
Clinodactyly
Permanent curving of the finger
0030084
Cortical cataract
0100019
Diplopia
Double vision
0000651
Distal amyotrophy
Distal muscle wasting
0003693
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Dysarthria
Difficulty articulating speech
0001260
Emotional lability
Emotional instability
0000712
Ependymoma
0002888
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Epiretinal membrane
0100014
Facial palsy
Bell's palsy
0010628
Foot dorsiflexor weakness
Foot drop
0009027
Genu valgum
Knock knees
0002857
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hemiparesis
Weakness of one side of body
0001269
Hoarse voice
Hoarseness
Husky voice

[ more ]

0001609

Cause

Neurofibromatosis type 2 is caused by a NF2 gene that is not working correctly.[1] Genetic changes known as DNA variants can impact how genes work. Pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.

Diagnosis

The diagnosis of neurofibromatosis type 2 (NF2) is based on clinical exam, the symptoms, and imaging studies. Genetic testing for a change (variant) in the NF2 gene may be helpful.[1] Diagnostic criteria for this condition is available.[5][6]

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 2 (NF2) is based on managing the signs and symptoms present in each person. Surgery and gamma knife procedures may be used to treat and remove vestibular schwannomas.[7] Other tumors associated with NF2 may also be treated surgically, although chemotherapy and/or radiation therapy may also be recommended.[1][8]

    Specialists involved in the care of someone with NF2 include:

    • Dermatologist
    • Neurologist
    • Otolaryngologist
    • Ophthmalogist
    • Audiologist
    • Oncologist
    • Medical geneticist

    Management Guidelines

    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      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 2. 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 2. Click on the link to view a sample search on this topic.

            References

            1. Evans DG. Neurofibromatosis 2. GeneReviews. Updated March 15, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1201/.
            2. Ardern-Holmes S, Fisher G, North K. Neurofibromatosis type 2: Presentation, Major Complications, and Management, with a focus on the pediatric age group. J Child Neurol. Jan 2017; 32(1):9-22. https://www.ncbi.nlm.nih.gov/27655473.
            3. Halliday D, Parry A, Evans DG. Neurofibromatosis type 2 and related disorders. Curr Opin Oncol. Nov 2019; 31(6):562-567. https://www.ncbi.nlm.nih.gov/pubmed/31425178.
            4. Evans DG. Neurofibromatosis type 2. Handb Clin Neurol. 2015; 132:87-96. https://pubmed.ncbi.nlm.nih.gov/26564072.
            5. Smith MJ, Bowers NL, Bulman M, Gokhale C, Wallace AJ et al. Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis [published correction appears in Neurology. 2017 Jul 11;89(2):215].. Neurology. 2017;88(1):87-92.. 2017; 88(1):87-92. https://pubmed.ncbi.nlm.nih.gov/27856782.
            6. Evans DG, King AT, Bowers NL, et al. Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing.. Genet Med. 2019;21(7):1525-1533.. 2019; 21(7):1525-1533. https://pubmed.ncbi.nlm.nih.gov/30523344.
            7. Lu VM, Ravindran K, Graffeo CS, et al. Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: a systematic review and meta-analysis of treatment outcomes. J Neurooncol. 2019; 144(2):239-248. https://pubmed.ncbi.nlm.nih.gov/31254266.
            8. Evans DG. Neurofibromatosis type 2. UpToDate. April 2015;
            9. Slattery WH. Neurofibromatosis type 2. Otolaryngol Clin North Am. Jun 2015; 48(3):443-60. https://pubmed.ncbi.nlm.nih.gov/26043141.

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