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Neurofibromatosis Type 2

Summary

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  • Autosomal dominant tumour predisposition syndrome, also termed NF2-related schwannomatosis
  • Caused by mutations in the NF2 gene, which encodes the tumour suppressor merlin (schwannomin)
  • Hallmark is bilateral vestibular schwannomas, with multiple meningiomas, schwannomas and ependymomas1

Pathophysiology

  • Mutation in the NF2 gene on chromosome 22q12
  • NF2 gene encodes merlin (schwannomin), a tumour suppressor protein
  • Loss of merlin function leads to:
    • Loss of contact-dependent growth inhibition
    • Development of multiple nervous system tumours (schwannomas, meningiomas, ependymomas)

Demographics

  • Incidence: approximately 1 in 25,000 to 33,000 live births
  • No ethnic or gender predilection
  • Roughly half of cases are inherited and half arise from de novo mutations
  • Typically presents in the second or third decade

Diagnosis

  • Clinical diagnosis based on the Manchester criteria, met by any of:
    • Bilateral vestibular schwannomas
    • First-degree relative with NF2 plus a unilateral vestibular schwannoma, or any two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacity
    • Unilateral vestibular schwannoma plus any two of the above features
    • Multiple meningiomas plus a unilateral vestibular schwannoma or any two of the above features
  • Genetic testing for NF2 gene mutations

Imaging

  • MRI with contrast is the modality of choice:
    • Bilateral vestibular schwannomas — enhancing cerebellopontine angle and internal auditory canal masses
    • Multiple meningiomas, both intracranial and spinal
    • Non-vestibular cranial nerve schwannomas
    • Spinal cord ependymomas and schwannomas
  • CT:
    • Widening of the internal auditory canals
    • Calcified meningiomas

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  • A 20-year-old patient presented after a seizure.
  • MRI showed bilateral vestibular schwannomas and many meningiomas (optic nerve sheath [red arrow], anterior falx and left parietal region).

Treatment

  • Surveillance MRI for tumour development and growth
  • Surgical resection or stereotactic radiosurgery for vestibular schwannomas
  • Bevacizumab (anti-VEGF) can reduce vestibular schwannoma volume and improve hearing in selected patients
  • Hearing preservation and rehabilitation, including auditory brainstem implants

Differential diagnosis

Differential Diagnosis Distinguishing Feature
Neurofibromatosis type 1 Café-au-lait macules, cutaneous and plexiform neurofibromas, optic pathway gliomas; caused by the NF1 gene
Schwannomatosis (SMARCB1/LZTR1) Multiple non-vestibular schwannomas without bilateral vestibular schwannomas
Sporadic vestibular schwannoma Unilateral, no other syndromic tumours or family history
Meningiomatosis Multiple meningiomas without vestibular schwannomas or an NF2 mutation
Solitary meningioma Single dural-based mass without associated schwannomas

  1. Asthagiri et al. Neurofibromatosis type 2. 2009. Lancet (London, England) - Open in new tab. ↩