Neurofibromatosis type 2 (NF2)-related schwannomatosis
NF2-related schwannomatosis, formerly called NF-2, is a genetic disorder that leads to tumors forming on cranial nerves and in the brain or spinal cord.
NF2-related schwannomatosis is caused by pathogenic variants in the NF2 gene, which encodes a tumor suppressor protein called Merlin. This protein plays an important role in regulating the way cells grow and develop their overall shape.
UCSF is the only hospital in California recognized by the Children’s Tumor Foundation as both an NF-1 and schwannomatosis comprehensive center. Our pediatric and adult clinics work closely together to provide lifelong specialized care for patients with all types of schwannomatoses. Our multidisciplinary team includes experts across neuro-oncology, neurosurgery, radiation oncology, medical genetics, neuropathology, and otolaryngology.
NF2-related schwannomatosis can result in patients developing different types of central nervous and peripheral system tumors including1:
- Schwannomas, typically located on the vestibulocochlear nerve (vestibular schwannomas) or on other cranial nerves
- Intracranial meningiomas
- Tumors in the spinal cord, including ependymomas, schwannomas, or meningiomas
Symptoms depend on where the tumor is located. For example, patients with bilateral vestibular schwannomas include:
- Hearing loss
- Tinnitus (ringing in the ears)
- Loss of balance or dizziness
- Facial weakness
Other symptoms of NF2-related schwannomatosis can include cataracts and skin lesions.
NF2-related schwannomatosis is less common than NF-1, occurring in approximately 1 in 25,000 people.2 Unlike NF1, NF2-related schwannomatosis is more commonly diagnosed in adults, with patients often receiving a diagnosis of the condition in their 20s.
About half of the people living with the condition inherited it from one of their parents. NF2-related schwannomatosis is an autosomal dominant disorder. This means if a child inherits a pathogenic variant of the NF2 gene (located on chromosome 22) from one parent, they will be affected by the disorder. However, the pathogenic variants that cause NF2-related schwannomatosis can arise spontaneously, and most patients are the first in their family to be diagnosed with the condition.3
NF2-related schwannomatosis is the most common form, but the term schwannomatosis refers to several other genetic conditions that cause tumors to form in the central and peripheral nervous system.
Pathogenic variants in the SMARCB1 or LZTR1 genes (located on chromosome 22) can cause these other types of schwannomatosis1. Some patients with schwannomatosis carry other pathogenic variants on chromosome 221. In other cases, there may not be a pathogenic genetic variant associated with their condition1.
Patients with these other types of schwannomatosis often experience pain related to where their tumor is located.
Unfortunately, there is no cure for NF2-related schwannomatosis. Since each individual presents with different symptoms of NF2-related schwannomatosis, the condition does not have a one-size-fits-all treatment.
Patients with NF2-related schwannomatosis have a higher risk of developing central and peripheral nervous system tumors, including schwannomas and ependymomas. Depending on the type, location, and size, some tumors can simply be monitored for additional growth or surgically removed. First-line treatment with radiation is typically not recommended4.
Since meningiomas are also common in patients with NF2-related schwannomatosis, our team works closely with UCSF’s multidisciplinary meningioma clinic.
Vestibular schwannomas are sometimes inoperable because they cannot be separated from the functioning portion of the nerve. In these cases, targeted drug therapy with the angiogenesis inhibitor bevacizumab or another targeted therapy such as brigatinib may be a treatment option to improve hearing5.
Neurocognitive rehabilitation is also available through our Neurocognitive Care Services. Our multidisciplinary team will assess each patient's needs and devise an individualized plan to improve language, motor, or cognitive impairments caused by NF2-related tumors.
The symptoms of NF2-related schwannomatosis and their severity differ from person to person, depending on the specific NF2 gene variants as well as additional genetic modifier variants they carry.
NF2-related schwannomatosis is a lifelong condition that requires monitoring to manage the symptoms a patient may experience over the course of their life as well as the increased risk of developing cancer. Patients should have routine imaging scans as well as ophthalmological and hearing exams.
In general, individuals with NF2-related schwannomatosis have shorter lifespans than people without this condition, but the prognoses and survival rates vary greatly depending on what type of tumor an individual may develop.
- Plotkin, S. R., et al. (2022). Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation. Genetics in medicine: official journal of the American College of Medical Genetics, 24(9), 1967–1977.
- Evans, D. G, et al. (2018). Schwannomatosis: a genetic and epidemiological study. Journal of neurology, neurosurgery, and psychiatry, 89(11), 1215–1219.
- Forde, C., et al. (2024). NF2-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study. Journal of medical genetics, 61(9), 856–860.
- Evans, D. G., et al. (2023). Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression. Neuro-oncology advances, 5(1), vdad025.
- Plotkin, S. R., et al. (2023). Multicenter, prospective, phase II study of maintenance bevacizumab for children and adults with NF2-related schwannomatosis and progressive vestibular schwannoma. Neuro-oncology, 25(8), 1498–1506.
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This content was reviewed by Brian Na, MD, PhD.
