Neurofibromatosis type 2, or NF2, is a rare genetic disorder impacting the nervous system. It is characterized by the development of noncancerous tumors, primarily along nerves in the brain and spinal cord. Though benign, their growth can lead to various health challenges. The disorder manifests during adolescence or early adulthood, though symptoms can appear at any age.
Genetic Causes and Inheritance
NF2 arises from a mutation within the NF2 gene on chromosome 22. This gene produces merlin (also known as schwannomin), a tumor suppressor protein that regulates cell growth. When the NF2 gene mutates, merlin is non-functional or absent, leading to tumor formation.
The condition can be inherited from a parent in an autosomal dominant pattern. If one parent has NF2, each child has a 50% chance of inheriting the mutated gene. About half of all NF2 cases are inherited; the other half result from a new, spontaneous mutation in the NF2 gene, occurring during early development in individuals with no family history.
Signs and Symptoms
The most characteristic feature of NF2 is the bilateral development of vestibular schwannomas, affecting the vestibulocochlear nerves (cranial nerve VIII). These nerves transmit sound and balance from the inner ear. As these tumors grow, they can exert pressure, leading to progressive hearing loss, often beginning unilaterally. Patients may also experience tinnitus and problems with balance and coordination.
Other tumor types frequently develop. Schwannomas can appear on other cranial nerves, like the trigeminal nerve (V), causing facial numbness or weakness. They may also form on peripheral nerves throughout the body, causing pain or weakness. Meningiomas, tumors of the meninges (membranes surrounding the brain and spinal cord), are also common.
Ependymomas can develop within the spinal cord, causing pain, weakness, or sensory changes in the trunk and limbs. Ocular manifestations are common, including specific cataracts like posterior subcapsular cataracts, often appearing early. Symptom range and severity can differ considerably among individuals, even within the same family.
The Diagnostic Process
Diagnosing NF2 involves a combination of clinical evaluation, imaging studies, and genetic testing. It begins when individuals present with hallmark symptoms, like progressive hearing loss or balance issues. A clinical assessment identifies characteristic signs and symptoms, guiding further diagnostic steps.
Imaging studies confirm tumor presence and extent. Brain MRI is important for visualizing vestibular schwannomas and other cranial nerve tumors. MRI of the spine is also performed to detect spinal schwannomas, meningiomas, and ependymomas. These images map tumor location and size throughout the central nervous system. The visualization of bilateral vestibular schwannomas on MRI is a strong indicator of NF2.
Genetic testing provides definitive confirmation by identifying a mutation in the NF2 gene. This analysis pinpoints the specific genetic alteration responsible for the condition. Healthcare providers utilize established diagnostic criteria, such as the Manchester criteria, to diagnose. These criteria integrate clinical findings, imaging results, and genetic testing outcomes to ensure an accurate diagnosis.
Approaches to Management and Treatment
No cure exists for NF2; management focuses on addressing tumor growth and alleviating associated symptoms. A primary strategy involves careful surveillance, known as a “watch and wait” approach. This entails regular annual MRI scans of the brain and spine to monitor tumor size and growth rate. This allows for timely intervention if tumors cause significant symptoms or threaten neurological function.
Surgical intervention is considered when tumors grow or cause severe symptoms. Surgery aims to remove as much of the tumor as safely possible while preserving neurological function. For vestibular schwannomas, surgeons aim to maintain hearing and facial nerve function, though this can be challenging depending on tumor size and location. Surgical approaches are tailored to the specific tumor type and its proximity to delicate neural structures.
Radiation therapy offers a non-invasive option for managing tumor growth. Stereotactic radiosurgery, a focused form of radiation, delivers a precise dose to the tumor, aiming to stop or slow its progression. This technique is used for vestibular schwannomas not amenable to surgery or for residual tumors after surgery. The precision of radiosurgery helps minimize damage to surrounding healthy tissues.
Medical therapies are a newer avenue. Bevacizumab, a targeted medication, has shown promise in some individuals by shrinking vestibular schwannomas and improving hearing. It works by inhibiting new blood vessel formation tumors need to grow. While not effective for all patients, it provides an alternative for those whose tumors are progressing.
Symptomatic treatment also addresses challenges like hearing loss. Auditory Brainstem Implants (ABIs) or cochlear implants can be considered for significant hearing impairment to restore some auditory perception.