Neurofibromatosis Type II

Original Editor - Wendy Walker

Lead Editors  

Clinically Relevant Anatomy

NF2 is inherited as an autosomal dominant condition, although half of affected individuals have NF2 as a result of a new (de novo) gene mutation. The manifestations of NF2 result from mutations in (or, rarely, deletion of) the NF2 gene, located on the long arm of chromosome 22. Affected individuals need only 1 mutated or deleted NF2 gene to exhibit signs of the condition.

The NF2 gene product known as merlin serves as a tumour suppressor; decreased function or production of this protein results in a predisposition to develop a variety of tumors of the central and peripheral nervous systems.

Mechanism of Injury / Pathological Process

NF2 is an autosomal dominant genetic disorder caused by mutations on chromosome 22. Patients usually have multiple Central Nervous System tumors, but the presence of bilateral Acoustic Neuromas, AKA vestibular schwannomas, is generally considered to be the hallmark of the disease.

NF2 is caused by mutations of the "Merlin" gene which influences the form and movement of cells. The principal treatments consist of neurosurgical removal of the tumors and surgical treatment of the eye lesions.

Histological findings in NF2 tumors have shown several important and distinct characteristics in this population as opposed to non-

NF2 Acoustic Neuromas. Depending on the severity of the underlying mutation, multiple other CNS tumors can also be found, notably meningiomas, schwannomas, and gliomas, some of them involving cranial nerves.

Clinical Presentation

Presenting symptoms

These may include the following:

• Hearing loss, ringing in the ears, and balance problems associated with vestibular nerve lesions
• Visual deficits
• Cranial nerve palsies

NF2 is associated with significant morbidity and decreased life span. Furthermore, diagnosis in childhood is often difficult because of the absence of central nervous system (CNS) involvement at a young age.

Although the genetic change causing NF2 is present at conception, the clinical manifestations occur over many years. The typical age of onset of symptoms is in the late teens to early 20s, but the age range covers the entire life span.

Complications of NF2

The following complications frequently occur:

Unilateral or, frequently, bilateral vestibular schwannomas leading to tinnitus, hearing loss, and/or problems with balance

Dumbbell-shaped spinal cord schwannomas are quite common in NF2 and result in significant morbidity; they present a great therapeutic challenge. Spinal cord ependymomas, astrocytomas, and meningiomas also occur, but less frequently. Intracranial meningiomas, on the other hand, are a frequent finding; they may be asymptomatic, or they may cause a variety of symptoms and CNS deficits.
Gliomas, ependymomas, and other cerebral, cerebellar, or spinal cord lesions that may result in neurologic deficits, seizures, and/or hydrocephalus
Peripheral nerve schwannomas, mixed tumors, and, occasionally, neurofibromas
Peripheral neuropathies
Visually significant juvenile cataracts

Nonvestibular schwannomas occur in more than half of patients and are often diagnosed in patients with an earlier age at diagnosis of NF2. Cranial nerves III and V are most commonly involved, but the rare occurrence of jugular foramen schwannomas potentially impacting the glossopharyngeal, vagus, and/or spinal accessory nerves may lead to dysphagia, esophageal dysmotility, hoarseness, or aspiration.

Diagnostic Procedures

Clinical diagnosis of NF2 requires that an individual present with at least 1 of the 3 following disease indications:

1. Bilateral eighth nerve masses visualized on MRI scan, using thin cuts, with and without gadolinium and on axial and coronal views
2. First-degree relative with documented NF2 for an individual with a unilateral eighth nerve mass, imaged as already described
3. First-degree relative with documented NF2 for an individual with at least 2 of the following findings: meningioma, glioma, schwannoma, juvenile cataract

However, because approximately half of cases result from new mutations, family history is often negative.

Diagnosis of NF2 involves the following:

Genetic testing
Imaging studies
Auditory, ophthalmic, and histologic examinations

Management / Interventions

Medical care for patients with NF2 consists of routine examinations focusing on early detection of some of the potential complications related to CNS or spinal cord lesions.

Guidelines for the care of the patient with NF2:

Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression
Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations
Annual MRI to monitor existing lesions or look for presymptomatic lesions
Annual ophthalmologic evaluations to monitor visual acuity
Treatment of symptomatic tumors is as follows:

Surgical resection represents the most common approach to clinically significant lesions
Rarely, radiation and/or chemotherapy may be recommended

Differential Diagnosis

Neurofibromatosis Type 1 (NF1) differs from NF2 in that NF1 patients have large numbers of skin lesions, whereas NF2 patients generally have fewer skin lesions.

Brainstem Gliomas

Intracranial Ependymomas

Physiotherapy

Customized vestibular rehabilitation incorporating adaptation, habituation, balance and mobility has been demonstrated to improve balance in patients with Acoustic Neuroma.

If the Facial Nerve is affected, causing facial palsy, then physiotherapy is indicated, as set out on the Facial Palsy page.

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