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  Disease summary:

  
  
  
  
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    Vestibular schwannomas (formerly known as acoustic neuromas) are benign tumors arising from the vestibular branch of the VIII cranial nerve. Vestibular schwannomas (VS) are usually isolated tumors, but can occur as part of neurofibromatosis 2 tumor suppressor syndrome (NF2).

    
    
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    The most common presenting symptom of VS is unilateral hearing loss, often noticed when using the phone. Tinnitus, imbalance, and facial nerve dysfunction can also occur.

    
    
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    NF2 is a hereditary condition associated with presence of bilateral vestibular schwannomas (BVS), schwannomas of other cranial and peripheral nerves, meningiomas, gliomas (spinal ependymomas), and posterior subcapsular cataracts (Table 154-1).

    
    
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    The National Institutes of Health (NIH) diagnostic criteria for NF2 requires presence of BVS, or a first-degree family member with NF2 plus unilateral VS or two other NF2-associated features as detailed in Table 154-2. The modified diagnostic criteria were expanded to include patients with presumed NF2 who not yet meet NIH diagnostic criteria.

    
    
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    Average age of onset of NF2 is usually in the early 20s. Earlier age of onset is associated with heavier tumor burden and more severe disease.

    
    
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    About 25% to 30% of founders with bilateral VS are found to be mosaic for mutation in the NF2 gene.

    
    
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    The likelihood of meeting criteria for NF2 after being diagnosed with a unilateral VS is inversely proportional to the age at diagnosis of the VS (Table 154-3).

  
  
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  Hereditary basis:

  
  
  
  
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    Sporadic VS are not associated with higher recurrence rates in family members, although patients with NF2 may present with unilateral VS, prior to developing other tumors.

    
    
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    NF2 is an autosomal dominant condition, which gives an affected individual a 50% risk of passing the condition to their children.

    
    
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    NF2 is fully penetrant, meaning that individuals inheriting the mutated NF2 gene will develop symptoms in 100% of the cases.

  
  
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  Monogenic forms:

  
  
  
  
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    NF2 is caused by mutations in the NF2 gene on chromosome 22.

    
    
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    The NF2 gene codes for a cytoskeleton protein named merlin, and is involved in cell growth regulation.

    
    
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    NF2 is a classic tumor suppressor syndrome, requiring both copies of the NF2 gene to be inactivated in the cell for tumor formation. In patients with NF2, the first NF2 inactivation event is either inherited or occurs early in embryogenesis and is present in all cells of the body. The second inactivating event occurs in somatic cells and leads to formation of schwannomas, meningiomas, and ependymomas, depending on the type of cell involved.

    
    
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    Loss of NF2 has been associated with sporadic VS formation. In sporadic tumors, both NF2 inactivating events occur at the cellular level, with no NF2 mutations found in nontumor tissues.

  
  
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  Family history:

  
  
  
  
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    Children of patients with nonmosaic NF2 have a 50:50 risk of inheriting the disease. Siblings of patients with NF2 who have clinically unaffected parents are at a higher risk of developing NF2 than the general population due to the risk of low-level gonadal mosaicism in one of the parents. In practice, we find the risk of gonadal mosaicism to be small in unaffected parents of NF2 patients.

  
  
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  Environmental factors:

  
  
  
  
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    There are no specific environmental factors associated with NF2 or VS formation. Although cell phone use has been suggested to be associated with an increased risk for brain tumor formation, no definitive research to date has found an association between VS and cell phone use. For patients with NF2, excessive use of radiation for diagnostic or therapeutic purposes should be avoided based on the theoretical risk of inducing tumor formation in patients with a tumor suppressor syndrome. Magnetic resonance imaging (MRI) scans are preferred to computed tomographic (CT) scans or x-rays when imaging is needed, particularly in children.

  
  
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  Differential diagnosis:

  
  
  
  
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    Schwannomatosis (multiple central and peripheral schwannomas without VS, intradermal schwannomas, or any other NF2-associated tumors); multiple meningioma syndrome (two or more intracranial meningiomas without other clinical stigmata of NF2).

Diagnostic Criteria

Clinical Characteristics