Full NF2-related schwannomatosis

NF2-related schwannomatosis (formerly known as Neurofibromatosis type 2, or NF2) is a rare genetic disorder characterized by the development of benign (noncancerous) tumors of the nervous system, most notably bilateral vestibular schwannomas (also called acoustic neuromas) that grow on the eighth cranial nerves responsible for hearing and balance. The condition is caused by pathogenic variants in the NF2 gene located on chromosome 22q12.2, which encodes the tumor suppressor protein merlin (also called schwannomin). Loss of merlin function leads to uncontrolled growth of Schwann cells, the cells that form the protective myelin sheath around nerves. In addition to bilateral vestibular schwannomas, individuals with NF2-related schwannomatosis frequently develop other nervous system tumors including meningiomas, ependymomas, and schwannomas of other cranial, spinal, and peripheral nerves. Key clinical features include progressive hearing loss (often the earliest symptom), tinnitus (ringing in the ears), balance difficulties, facial weakness or paralysis, and visual problems such as cataracts (particularly juvenile posterior subcapsular lenticular opacities). Spinal tumors may cause pain, numbness, weakness, or other neurological deficits depending on their location. Skin manifestations can include subcutaneous schwannomas and skin plaques. The disease typically presents in the late teenage years or early adulthood, though onset can range from childhood to later in life. Approximately 50% of cases are inherited from an affected parent, while the remaining cases arise from de novo (new) mutations. Management is multidisciplinary and includes regular surveillance with MRI imaging, audiological monitoring, and ophthalmological examinations. Treatment options include surgical removal of tumors, stereotactic radiosurgery, and conventional radiation therapy, though decisions must carefully weigh the risks of treatment against tumor progression. The FDA-approved MEK inhibitor selumetinib and the anti-VEGF monoclonal antibody bevacizumab have shown promise in reducing tumor size and preserving hearing in some patients, though no curative therapy currently exists. Ongoing clinical trials continue to explore targeted molecular therapies.

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