Handbook of Genetic Counseling/Neurofibromatosis - Type 2

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Neurofibromatosis - Type 2


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  • Disease characteristics
    • Genetic disorder that causes tumors to grow on various nerves
    • Also affects other tissues such as bones and skin
    • Two distinct types: NF-1 and NF-2
  • Inheritance
    • Autosomal dominant
    • Affected individuals have 50% chance of passing on mutation to each of their children
    • Half of affected individuals have de novo mutations
    • If neither parent has NF2, recurrence risk is very low - only one case of germline mosaicism reported
    • Uniform age of onset within families
  • Molecular genetics
    • Caused by mutation in the NF2 gene
    • Located at 22q12
    • Normal gene product is schwannomin or merlin
      • Homology to 4.1 family of cytoskeletal associated proteins
      • Has role in prevention of schwannoma formation
      • Tumor suppressor gene
  • Incidence is 1 in 40,000 people

Clinical Features and Natural History

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  • Some variability in clinical manifestations
    • Variability within families is low
    • Suggests strong genotype-phenotype correlation
  • Average age of onset of symptoms is 18-24
    • Some people don't develop signs until their 40's or 50's
    • Considered adult-onset so may be underdiagnosed in children
    • Nonsense and frame shift mutations more severe
  • Bilateral vestibular schwannoma (acoustic neuroma)
    • Affect almost all patients with NF2
    • Tumor that arises from Schwann cells that support and protect nerves with insulation needed to conduct information on 8th cranial nerve
    • Initial symptoms include tinnitus (ringing in ears), hearing loss, and balance dysfunction
    • May result in hearing loss in one or both ears
  • Spinal tumors (>66%)
    • Include schwannomas that may cause numbness in part of body
    • Intramedullary tumors such as astrocytoma and ependymoma (5-33%)
    • Most individuals with spinal cord tumors have more than one
  • Meningiomas (50%)
    • Tumor that grows from cells that line the brain and spinal cord in protective sheets called meninges
    • May be intracranial or spinal
    • Cause different neurological symptoms depending on location
  • Ocular involvement (33%)
    • Cataracts
      • Known as juvenile posterior sublenticular opacity
      • May impair vision if not removed
    • Optic gliomas
      • Tumors on vision nerve
      • May lead to blindness
  • Other features
    • Other types of central nervous system tumors
    • Atypical café-au-lait spots
    • Cutaneous neurofibromas
  • Somatic mosaicism
    • Suspected in individuals with unilateral vestibular schwannoma and multiple other tumors on one side
    • More difficult to diagnose
  • Considerably shortened lifespan
    • Average age of death is 36 years
    • With improvements in diagnosis, monitoring, and surgery this is changing

Diagnosis/Testing Options

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  • Clinical diagnosis
    • Bilateral VIII nerve mass on CT or MRI (vestibular schwannomas)


    • First degree relative with NF2 and either
      • Unilateral 8th nerve mass


      • Two of the following
        • Meningioma
        • Glioma
        • Schwannoma
        • Juvenile posterior subcapsular lenticular opacity
  • Mutation analysis
    • Mutations identified in 65-80% of patients with clinical diagnosis
    • Testing provided by Athena Diagnostics/Mass Gen
    • Includes SSCP (single stranded conformational polymorphism)
    • May take up to 6 months for results
    • Costs about $2700
    • Considered appropriate to test unaffected at risk children and adults
  • Linkage analysis
    • Appropriate if more than one affected family member
    • Doesn't work for 50% of patients with de novo mutations
    • High accuracy because markers are very closely linked
  • Prenatal testing
    • Available for fetuses at 50% risk or greater
    • Can be performed if mutation identified in affected family member
    • Requires cells obtained from CVS or amniocentesis


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  • Currently is no cure or treatment
  • Early recognition allows for earlier intervention and improved outcome
  • Begin screening in early teens
    • ABR and MRI exams for vestibular schwannomas
      • Surgery generally successfully preserves hearing is tumors small
      • Should begin learning sign language before hearing is lost
      • Hearing aids may help preserve hearing early on
    • Routine complete eye examinations
    • Routine neurological examinations
    • Intracranial, cranial nerve, and spinal tumors often slow growing

Differential Diagnosis

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  • NF1
    • Has Lisch nodules, axillary and inguinal freckling, and plexiform neurofibromas not seen in NF2
    • Patients with NF2 do not have mental retardation or learning problems
  • Unilateral vestibular schwannoma
    • Accounts for 5-10% of intracranial tumors
    • Less than 5% are bilateral and associated with NF-2
  • Schwannomatosis
    • Multiple schwannomas without vestibular schwannomas
    • Develop intracranial, spinal nerve root, or peripheral nerve tumors
  • Multiple meningiomas
    • Without vestibular schwannomas
    • Typically occur in older adults

Psychosocial Issues

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  • Feelings of fear, anger, shock, denial over new diagnosis
  • Difficulty adjusting to loss of hearing
  • Burden of condition requiring extensive surveillance
  • Anxiety about possibility of shortened life span
  • Survivor guilt, transmitter guilt
  • Support system to help cope with diagnosis

Support Resources

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  • National Neurofibromatosis Foundation
95 Pine Street, 16th Floor
New York, NY 10005
Phone: 800-323-7938
Web: www.nf.org
  • Neurofibromatosis, Inc
8855 Annapolis Road, Suite 110
Lanham, MD 20706-2924
Phone: 410-461-5213
Web: www.nfinc.org
  • The Acoustic Neuroma Association
PO Box 12402
Atlanta, GA 30355
Phone: 404-237-2704
Web: ANAUSA@aol.com


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  • GeneReviews. "Neurofibromatosis 2" (2002).
  • "Neurofibromatosis Type 2: Information for Patients and Families." National Neurofibromatosis Foundation brochure.


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The information in this outline was last updated in 2001.