Neurofibromatosis 2 (NF2)

View Details

Status

Done

Parent item

Schwannoma Predisposition Syndromes (SPS)

Diagnostic criteria for NF2

• Old Manchester criteria (either one of the 4)
1. Bilateral vestibular schwannomas (VS) on imaging (MRI or CT)
2. A first degree relative (parent, sibling, or offspring) with NF2 +
• Unilateral VS
• OR any TWO of the following:
• Meningioma
• Schwannoma (including spinal root)
• Glioma (includes astrocytoma, ependymoma)
• Posterior subcapsular lens opacity
• Cortical wedge cataract
3. Unilateral VS +
• Any TWO of the following:
• Meningioma
• Schwannoma (including spinal root)
• Glioma (includes astrocytoma, ependymoma)
• Posterior subcapsular lens opacity
• Cortical wedge cataract
4. Multiple meningiomas +
• ONE of the following
• Unilateral VS
• OR any TWO of the following:
• Meningioma,
• Schwannoma (including spinal root),
• Glioma (includes astrocytoma, ependymoma),
• Posterior subcapsular lens opacity, or
• Cortical wedge cataract
• NB: those with suspicious findings should have molecular gene testing
• identification of a heterozygous pathogenic variant of the NF2 gene.

General

• AKA
• MISME syndrome (Multiple Inherited Schwannomas, Meningiomas, and Ependymomas)
• Bilateral acoustic Vestibular Schwannoma

• Despite its name, is not associated with neurofibromas
• 10x less common than NF1

• 50% have a multiple meningioma.

• By 30 yrs old, almost 100% have bilateral VS
• Most NF2 patients will become deaf at some time during their life

• Pregnancy may accelerate the growth of eighth nerve tumours

• Two subtypes:
• More severe and more common form
• Younger age of onset (20-30 yrs)
• Rapid progression of hearing loss
• Multiple associated tumours
• Milder and less common form
• Presents later in life,
• Slower deterioration in hearing
• Fewer associated tumours

Numbers

• Incidence 1/25,000 - 1/40,000

• Prevalence: 1/210000

• Adult-onset disease,
• Age of onset is 18–24 years.
• By age 30 years, almost all affected patients will have bilateral VS

Genetics

• Autosomal dominant inheritance.

• There are a number of NF2 gene mutations that lead to the diagnosis of NF2.
• Most common is mutation at chromosome 22q12.2,→ inactivation of schwannomin (AKA merlin, a semi-acronym for moesin-, ezrin, and radixin-like proteins), a tumour suppression peptide.

• Nonsense and frameshift mutations are more likely to have intramedullary tumors (but not any other type of tumour) compared with other mutation types.

Other clinical features

• Seizures or other focal deficits

• Skin nodules, dermal neurofibromas, café au lait spots (less common than in NF1)

• Multiple intradural spinal tumours are common (less common in NF1)



• Ependymoma with haemosiderin caps
• Intramedullary (especially ependymomas)
• Extramedullary (schwannomas, meningiomas…)



 



• Meningiomas fq involve skull base causing dural sinus invasion

• Retinal hamartomas

• Antigenic nerve growth factor is increased (does not occur with NF1)

• NO SKELETAL DYSPLASIA

• NO LEARNING DISABILITIES
• Neoplasm arise from CNS coverings

Schwannomas

• Associated with NF2

• WHO grade I

• Occur at an earlier age (in the 20s) than sporadic (i.e., non-NF2 associated) schwannomas (in the 50s).

• Although cutaneous neurofibromas have been reported, in NF2 many of these turn out to be schwannomas on histological analysis.

Management

• Bilateral vestibular schwannomas:
• Chance of preserving hearing is best when the VS is small.
• Remove small VS first →
• If hearing in the operated ear is serviceable
• Remove the second tumour
• If hearing in the operated ear is not serviceable
• Follow the second tumour as long as possible → perform a subtotal removal in an attempt to prevent total deafness
• Stereotactic radiosurgery therapy may be a treatment option

• Prior to surgery, obtain MRI of cervical spine to R/O intraspinal tumours that may cause cord injuries during other operations