However, molecular analysis of the NF2 gene in schwannomatosis patients has shown the presence of inactivating mutations in the tumor cells, but no evidence of the germline mutations that are found in NF2 patients.A mechanism involving both the SMARCB1 and NF2 genes may be responsible for the development of the disease because tumor analysis of schwannomas indicates the presence of inactivating mutations in both the SMARCB1 and NF2 genes. However, there is speculation about the involvement of an unidentified schwannomatosis gene(s) in most cases. This is because one study found no SMARCB1 germinal mutations in patients with familial schwannomatosis. Some schwannomatosis patients do not have SMARCB1 or NF2 mutations. Furthermore, many patients exhibit somatic mosaicism for mutations in the NF2 or SMARCB1 gene, which means that some somatic cells have the mutation and some do not in the same patient. Ultimately, the tumorigenesis of schwannomas is not solely dependent on one gene locus alone. In regards to the SMARCB1 and NF2 genes, it is important to understand constitutional mutations and somatic mutations. Constitutional mutations are the first inactivation events that are often small mutations, such as point mutations and deletion/insertion of single base pairs. Somatic mutations are the second mutations that occur and may also be another small mutation or the loss of the remaining allele of the gene. Schwannomas from one patient share the same constitutional mutations but have distinct somatic mutations. In addition, the constitutional mutation may be present in non-tumor.SMARCB1 is also known as INI1, hSNF5, or BAF47.
Success rates, although limited in data, appear to be in the low to mid ninety percent range. As most schwannomas are benign, many doctors will take the “watch and wait” approach and leave the tumors alone until they start causing harmful side effects. Schwannomatosis patients have multiple tumors and the risks of having so many surgeries outweigh the benefits. Prognosis
Many of the symptoms of schwannomatosis overlap with NF2. Schwannomas occur instead of the neurofibromas that are hallmarks of neurofibromatosis Type 1 (NF1). Multiple schwannomas manifest throughout the body or in isolated regions. The schwannomas develop on cranial, spinal and peripheral nerves. Chronic pain, and sometimes numbness, tingling and weakness. About 1/3 of patients have segmental schwannomatosis, which means that the schwannomas are limited to a single part of the body, such as an arm, a leg or the spine. There are several cases where people with schwannomatosis have developed a vestibular schwannoma (acoustic neuroma). An acoustic neuroma is a schwannoma on the vestibular nerve in the brain. This nerve is involved in hearing and patients with vestibular schwannomas experience hearing loss. However, bilateral vestibular schwannomas (vestibular schwannomas on both sides of the brain) do not occur in schwannomatosis. Juvenile vestibular tumors do not occur either. Patients with schwannomatosis do not have learning disabilities related to the disease. Symptoms are sometimes brought on by hormonal changes such as puberty and pregnancy. == References ==