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Table 1. Diagnostic Criteria for NF2-Related SWN

Diagnosis of NF2-related SWN with one of the following:
• Bilateral vestibular schwannomas
• Identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, ependymoma, meningioma). If the
mutation is found in < 50% of unaffected tissue, such as blood, then the diagnosis is mosaic NF2-related SWN
Either 2 major or 1 major and 2 minor criteria:
Major Minor
• Unilateral vestibular schwannoma
• 1 -degree affected relative, other than sibling • Can count > 1 of a type: ependymoma, meningioma, dermal schwannoma
st
• 2 or more meningiomas • Can count only once: Juvenile subcapsular or cortical cataracts, retinal
• NF2 pathogenic variant in unaffected tissue, such as blood (< hamartoma, epiretinal membrane in a person < 40 years old, meningioma
50% frequency indicates mosaicism)
NF2-related SWN: Neurofibromatosis type 2-related schwannomatosis.

NF2-related SWN is frequently unrecognized in childhood, when patients may present with intradermal skin
lesions or ocular manifestations before developing or becoming symptomatic from intracranial tumors .
[17]
Ocular findings include early-onset cataracts, retinal hamartomas, thickened optic nerves, CN3 palsies,
epiretinal membranes, and retinal tufts on optical coherence tomography. Occasionally, a child may have a
mononeuropathy without a tumor or an isolated meningioma or schwannoma. Cognitive impairment is not
associated with NF2-related SWN [18-24] .

Historically, it has not been uncommon for individuals to progress to complete deafness. The average age of
death is 36 years; however, due to the Gardner (milder) versus Wishart (more severe) phenotype, outcomes
diverge. The Japanese Ministry of Health, Labor and Welfare maintains a National NF2 registry with a total
of 807 patients, 44% male and 56% female. In their cohort, the age of onset ranged from less than 5 years to
80 years, exemplifying the wide variability in presentations. Patients who presented before 25 years of age
had survival rates of 80%, 60%, and 28% at 5, 10, and 20 years, respectively. For patients who presented at 25
years of age or older, survival rates were 100%, 87%, and 62% at 5, 10, and 20 years, respectively [18,19,20,25] .
Clearly, the more symptomatic a person is, the earlier they present, and mortality is impacted.

Incidence and genetics
NF2-related SWN has an incidence of 1 in 25,000. It is an autosomal dominant disorder with 100%
penetrance. In patients with de novo mutations, the vast majority exhibit somatic mosaicism . Studies
[26]
estimate that about one-third of individuals with bilateral vestibular schwannomas, and up to 60% of those
with a unilateral vestibular schwannoma, have mosaicism. For individuals with germline mutations, there is a
50% risk of passing the gene to a child; for those with somatic mosaicism, the risk is substantially lower (1 in
8 to 1 in 12 for individuals with negative NF2 genetic testing). Children who present fulfilling clinical criteria
likely have a more severe phenotype due to the presence of a germline mutation [17,27] .

UPDATES
Just as our forefathers were confused by the differences between NF1 and NF2-related SWN, confusion
remains among some healthcare providers and patients or families. Some of this confusion was likely related
to nomenclature. To address this conundrum, a consensus was developed to further distinguish these
entities, leading to the formal recognition of NF1 and NF2-related SWN. International experts have since
modified the clinical criteria and incorporated genetic and molecular data. See Table 1 .
[28]

Surgical and radiation treatment
Surgery has been the mainstay of therapy for vestibular schwannomas for many years. Small vestibular
tumors (average size 1 cm, range 0-3 cm) can often be completely resected without compromising hearing or
facial nerve function. Surgery becomes more challenging for larger tumors when the facial nerve is intact and