NF2-related schwannomatosis
Autosomal dominant NF2 (merlin) gene disorder causing bilateral vestibular schwannomas, meningiomas, and juvenile cataracts; diagnosed by clinical criteria and MRI with gadolinium, and managed with hearing-preserving surgery, stereotactic radiosurgery, and bevacizumab for progressive schwannomas.
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What this article covers
- Overview
Definition: NF2-related schwannomatosis, formerly called neurofibromatosis type 2 (NF2), is an autosomal dominant tumor-predisposition syndrome caused by mutations in the NF2 gene, defined by…
- Epidemiology
Incidence: substantially rarer than NF1, occurring in roughly 1 in 25,000 to 1 in 33,000 births.
- Risk factors
Family history: an affected first-degree relative confers a 50% transmission risk per pregnancy given autosomal dominant inheritance.
- Pathophysiology
Gene and protein: the NF2 gene on chromosome 22q12 encodes merlin (also called schwannomin), a membrane-cytoskeleton linking protein that normally suppresses cell proliferation.
- Clinical features
Bilateral vestibular schwannomas: the hallmark finding; early compression of the vestibulocochlear nerve causes unilateral or asymmetric sensorineural hearing loss, tinnitus, and disequilibrium…
- Differential diagnosis
Neurofibromatosis type 1: presents with cafe-au-lait macules, cutaneous and plexiform neurofibromas, Lisch nodules, and optic glioma rather than bilateral vestibular schwannomas; caused by a…
- Diagnosis
What establishes the diagnosis: demonstration of bilateral vestibular schwannomas on MRI in a patient under age 70 establishes the diagnosis; in a patient with a family history of NF2-related…
- Management
First step after diagnosis: establish care with a multidisciplinary team (neurotology, neurosurgery, ophthalmology, and genetics), since there is no cure and treatment focuses on preserving hearing…
- Complications
Bilateral deafness: progressive bilateral hearing loss from vestibular schwannoma growth or from treatment itself is the most common functional complication.
- Prognosis
Life expectancy: reduced compared with the general population, historically related to brainstem compression and complications of multiple cranial nerve tumors, though outcomes have improved with…
- Prevention
No primary prevention: because NF2-related schwannomatosis arises from a germline or mosaic mutation, there is no way to prevent the disease itself.
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