Materiały źródłowe

• #1 Schwannomatoses related to genetic variants other than NF2 – UpToDate

  https://www.uptodate.com/contents/schwannomatoses-related-to-genetic-variants-other-than-nf2

  Schwannomatosis is the name originally coined for a neurocutaneous syndrome that is genetically distinct from neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). It was first recognized as distinct from NF2 in the late 1990s. […] In 2022, the nomenclature for NF2 and schwannomatosis was further updated to recognize the disorders as part of a spectrum of schwannoma predisposition syndromes with extensive clinical overlap, defined in many cases by pathogenic variants in one of several genes on chromosome 22: […] -related schwannomatosis (shortened to „NF2” in this topic and others for brevity), formerly neurofibromatosis type 2 […] -related schwannomatosis […] -related schwannomatosis.

• #2 Schwannomatosis | Neupsy Key

  https://neupsykey.com/schwannomatosis/

  Schwannomatosis is a newly recognized form of neurofibromatosis that is distinct from neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2), in terms of both its primary clinical features and its genetic basis. […] As this book went to press, it was not yet clear what gene or mechanism might be responsible for schwannomatosis. […] It is not yet clear what causes schwannomatosis. […] Part of the challenge in finding the responsible mechanism is that the inherited or familial version of schwannomatosis accounts for only 15% of cases; the remainder are sporadic cases that develop without a family history of the disorder. […] The hunt for the mechanism responsible for schwannomatosis has also been hindered by puzzling and contradictory findings when tumor samples were analyzed in the laboratory.

• #3 Schwannomatosis & NF2-Related Schwannomatosis | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/neurofibromatosis/schwannomatosis

  Schwannomatosis (shwah-NOH-muh-TOH-sis) is rare. Its linked to a higher risk of getting a type of tumor called schwannomas. Schwannomatosis affects 1 out of every 25,000 to 40,000 people. […] This condition can be caused by a change (mutation or variant) in a gene. […] Some people have mutations in the NF2 gene (chromosome 22). It can be inherited (passed on from parent to child). It also can happen in people whose parents do not have the mutation. […] About half of the people who have schwannomatosis have mutations in the genes SMARCB1 or LZTR1. These mutations can be inherited. […] More often, these mutations happen in people who did not inherit these gene mutations from their parents. Doctors are researching other mutations that may cause schwannomatosis.

• #4 Schwannomatosis – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/learn-about-nf/schwannomatosis

  Schwannomatosis is a rare form of neurofibromatosis that has only recently been identified. Affecting about 1 in 40,000 people, schwannomatosis causes the development of painful tumors called schwannomas usually on spinal and peripheral nerves. […] Symptoms, which typically occur in adulthood, often include chronic pain due to tumors pressing on nerves as well as neurological features such as tingling or numbness.

• #5 Schwannomatosis | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20563921/

  Schwannomatosis is caused by an altered gene. The specific genes involved depend on the type: […] NF2-related schwannomatosis (NF2). The NF2 gene produces a protein called merlin, also called schwannomin, that suppresses tumors. An altered gene causes a loss of merlin, leading to cell growth that’s not controlled. […] SMARCB1- and LZTR1-related schwannomatosis. So far, two genes are known to cause these types of schwannomatosis. Changes of the genes SMARCB1 and LZTR1, which suppress tumors, are linked with these conditions.

• #6 Schwannomatosis | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/schwannomatosis

  There are three types of schwannomatosis. Each type is caused by an altered gene. […] Schwannomatosis is caused by an altered gene. The specific genes involved depend on the type: […] NF2-related schwannomatosis (NF2). The NF2 gene produces a protein called merlin, also called schwannomin, that suppresses tumors. An altered gene causes a loss of merlin, leading to cell growth that’s not controlled. […] SMARCB1- and LZTR1-related schwannomatosis. So far, two genes are known to cause these types of schwannomatosis. Changes of the genes SMARCB1 and LZTR1, which suppress tumors, are linked with these conditions.

• #7 Schwannomatosis | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/schwannomatosis?content_id=CON-20563921

  This rare conditions causes slow-growing tumors on nerves, including on the nerve in the ear that carries sound information to the brain. […] Schwannomatosis is caused by an altered gene. The specific genes involved depend on the type: […] NF2-related schwannomatosis (NF2). The NF2 gene produces a protein called merlin, also called schwannomin, that suppresses tumors. An altered gene causes a loss of merlin, leading to cell growth that’s not controlled. […] SMARCB1- and LZTR1-related schwannomatosis. So far, two genes are known to cause these types of schwannomatosis. Changes of the genes SMARCB1 and LZTR1, which suppress tumors, are linked with these conditions.

• #8 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  NF2-related schwannomatosis is a tumor predisposition syndrome most commonly associated with the development of multiple schwannomas (classically bilateral vestibular schwannomas), meningiomas, and ependymomas. This disorder is caused by mutations in the neurofibromatosis 2 (NF2) gene, a tumor suppressor gene that encodes for merlin/schwannomin and is located on chromosome 22. […] NF2-related schwannomatosis is an autosomal dominant disorder caused by mutations of the neurofibromatosis 2 gene, a tumor suppressor gene located on chromosome 22, whose normal protein product is merlin/schwannomin. […] NF2-related schwannomatosis has also been called central or acoustic neurofibromatosis because of its characteristic involvement of the central nervous system (CNS) with tumors, especially meningiomas and acoustic neuromas that are now termed vestibular schwannomas.

• #9

  https://link.springer.com/article/10.1007/s00439-016-1753-8

  The diagnosis of schwannomatosis is predicated upon the molecular and/or clinical diagnostic criteria according to Plotkin et al. (2013) and Ostrow et al. (2016). […] These studies imply that germline SMARCB1 mutations are present in at least 48% of familial and 9.8% of sporadic schwannomatosis cases. […] Biallelic inactivation of SMARCB1 has been observed in both schwannomas and meningiomas of patients with schwannomatosis. […] Meningiomas occur in 5% of schwannomatosis patients and appear to be located predominantly in the cerebral falx. […] Recently, a patient with Coffin-Siris syndrome and schwannomatosis has been reported to carry a germline missense mutation in exon 9 of SMARCB1. […] The recognition that mutations in the SMARCB1 gene predispose to benign schwannoma, which usually become symptomatic during adulthood, came as something of a surprise.

• #10 Inheritance & Genetics – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/learn-about-nf/schwannomatosis/inheritance-genetics

  Although schwannomatosis is a genetic condition, the inheritance patterns for this disorder are complex and much less clear than for both NF1 and NF2. […] A mutation in a gene first identified in 2007 called SMARCB1 is associated with about 40% of familial cases and 10% of sporadic cases of schwannomatosis. […] Research conducted at the UAB Medical Genomics Laboratory which specializes in genetic studies for all forms of neurofibromatosis has recently led to the groundbreaking discovery of a new gene, called LZTR1, that helps to explain some familial and sporadic cases of schwannomatosis in people who dont have a mutation in the SMARCB1 gene. […] A sophisticated gene sequencing technique was used to identify the LZTR1 gene and to determine that a mutation in this gene predisposes individuals to develop schwannomatosis.

• #11 Inheritance & Genetics – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/learn-about-nf/schwannomatosis/inheritance-genetics

  Although schwannomatosis is a genetic condition, the inheritance patterns for this disorder are complex and much less clear than for both NF1 and NF2. […] A mutation in a gene first identified in 2007 called SMARCB1 is associated with about 40% of familial cases and 10% of sporadic cases of schwannomatosis. […] Research conducted at the UAB Medical Genomics Laboratory which specializes in genetic studies for all forms of neurofibromatosis has recently led to the groundbreaking discovery of a new gene, called LZTR1, that helps to explain some familial and sporadic cases of schwannomatosis in people who dont have a mutation in the SMARCB1 gene. […] A sophisticated gene sequencing technique was used to identify the LZTR1 gene and to determine that a mutation in this gene predisposes individuals to develop schwannomatosis.

• #12 Relief for Symptoms of Schwannomatosis | Dr. H. Weinberg

  https://www.hweinbergplasticsurgery.com/resources-info/schwannomatosis.html

  Half of the patients with Schwannomatosis have mutations in genes SMARCB1 or LZTR1. The mutations could be inherited, but they most often occur in people that do not have a family history of the disorder (sporadic Schwannomatosis). Only 15% of patients have the inherited form (familial Schwannomatosis). […] Medical researchers are trying to identify other gene mutations that could cause Schwannomatosis.

• #13 Neurofibromatosis and Schwannomatosis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/10495

  SWN is the rarest form of NF characterized by multiple schwannomas in the absence of bilateral vestibular schwannomas inherited via autosomal dominance in 15–20% […] Mutations in SMARCB1 and LZTR1 genes cause SWN. Causative inactivating germline mutations in the tumor suppressor genes SMARCB1 and LZTR1 are present in approximately 85% of families with SWN and up to 40% of sporadic cases. […] Mutations in the SMARCB1 or LZTR1 gene alone are not sufficient to trigger SWN and require additional somatic mutations. Genetic testing is available for both SMARCB1 and LZTR1. […] In SMARCB1 (INI1) mutation-positive schwannomas, there can be additional genetic alterations, including loss of one copy of chromosome 22 and inactivating mutations in the NF2 gene. […] This suggests a four-hit, three-step model of tumorigenesis in considerable SMARCB1-associated SWN patients.

• #14 Non-NF2-related schwannomatosis

  https://www.genturis.eu/l=eng/thematic-disease-groups/schwannomatosis-and-neurofibromatosis/non-nf2-related-schwannomatosis.html

  Pathogenic variants in SMARCB1, LZTR1 and possibly the DGCR8 genes can cause non NF2-related schwannomatosis. The proteins produced from these genes are thought to act as tumour suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in these genes may help cells grow and divide without control or order to form a tumour. […] Current genetic testing does not reveal a mutation in all affected individuals, and there may be additional genes responsible for the disorder in some people yet to be discovered. […] Studies suggest that 15 to 25 percent of cases of schwannomatosis run in families. These familial cases have an autosomal dominant pattern of inheritance, which means a mutation in one copy of the SMARCB1, LZTR1 or DGCR8 genes in each cell greatly increases the risk of developing schwannomas. However, some people who have an altered gene never develop tumours, which is a situation known as reduced penetrance. […] New alterations occurring in sperm or eggs can end up in every cell of the child and represent approximately 30% for LZTR1-related schwannomatosis and 10% for SMARCB1-related schwannomatosis.

• #15 La schwannomatose

  https://www.genturis.eu/l=fra/syndromes/neurofibromatoses/la-schwannomatose.html

  Mutations in SMARCB1 and LZTR1 can cause schwannomatosis. The proteins produced from both genes are thought to act as tumour suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in either of these genes may help cells grow and divide without control or order to form a tumour. SMARCB1 and LZTR1 are located on chromosome 22q, near the NF2 gene. […] Current genetic testing does not reveal a mutation in all affected individuals, and there may be additional genes responsible for the disorder in some people yet to be discovered.

• #16 How is Schwannomatosis (other) diagnosed? | Nerve Tumours UK

  https://nervetumours.org.uk/what-are-nerve-tumours/schwannomatosis/how-is-schwannomatosis-diagnosed

  Most people with Schwannomatosis are the only person in their family to be affected. […] The genetics of Schwannomatosis is much more complicated than in NF1 and NF2-related-Schwannomatosis. So far two genes have been identified; the first (called SMARCB1 or INI1) was identified in 2007 with the second LZTR1 being found in 2013. Mutations have been found in these genes in 60-70% of people from affected families cases, but in only about 20-25% of people who are the only person in the family. […] Schwannomas in NF2 and Schwannomatosis have different genetic changes and this is proving helpful in providing a clear diagnosis. However, it is likely that at least 3 more genes remain to be found.

• #17 Schwannomatosis: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/schwannomatosis/

  Schwannomatosis is a disorder characterized by multiple noncancerous (benign) tumors called schwannomas, which are a type of tumor that grows on nerves. Schwannomas develop when Schwann cells, which are specialized cells that normally form an insulating layer around the nerve, grow uncontrollably to form a tumor. […] Mutations in at least two genes, SMARCB1 and LZTR1, can cause schwannomatosis. The proteins produced from both genes are thought to act as tumor suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in either of these genes may help cells grow and divide without control or order to form a tumor. […] It appears that mutations in the SMARCB1 or LZTR1 gene alone are not enough to trigger the development of schwannomas. Additional genetic changes (somatic mutations) that are acquired during a person’s lifetime and are present only in certain cells may also be required for schwannomas to form. The most common somatic mutations in schwannomas are mutations in the NF2 gene and a loss of chromosome 22 (which is the chromosome on which the SMARCB1, LZTR1, and NF2 genes are found). […] Some people with schwannomatosis do not have an identified mutation in the SMARCB1 or LZTR1 gene. In these cases, the cause of the disorder is unknown. Researchers suspect that mutations in other as-yet-unidentified genes, most likely on chromosome 22, also contribute to this condition.

• #18 What Is Schwannomatosis?

  https://www.icliniq.com/articles/genetic-disorders/schwannomatosis

  Schwannomatosis occurs due to mutations in the two genes, SMARCB1 and LZTR1. The proteins produced in these genes help suppress the multiplication and growth of the cells in a disorderly fashion, and they are known as tumor suppressors. When these proteins are not produced due to abnormalities, the cells start to grow and divide rapidly to form a tumor. […] It is said that mutations in the SMARCB1 and LZTR1 genes are not enough to trigger schwannomas, but some additional somatic changes that have been acquired in the life of an individual also trigger schwannomas. The common somatic mutation that causes schwannomas is the mutation in the NF2 gene and a loss of chromosome 22 as SMARCB1, LZTR1, and NF2 genes rely on chromosome 22. In some cases, schwannomatosis does occur in people who do not have identified mutations in LZTR1 and SMARCB1 genes. In such cases, the cause of the disorder is still unknown.

• #19

  https://link.springer.com/article/10.1007/s00439-016-1753-8

  Thus, schwannomatosis is paradigmatic for a tumour predisposition syndrome caused by the concomitant mutational inactivation of two or more tumour suppressor genes. […] So far, two schwannomatosis predisposition genes have been identified, SMARCB1 and LZTR1. […] The majority of patients with schwannomatosis are sporadic, whereas 13-25% are familial cases. […] A combination of linkage analysis in affected families and mutation screening of the NF2 gene in schwannomas indicated that schwannomatosis is not due to germline mutations in the NF2 gene. […] However, instead of constitutional (germline) NF2 mutations, independent somatic mutations affecting both NF2 alleles are frequently found in schwannomas of patients with schwannomatosis. […] The clinical overlap between schwannomatosis and NF2 renders differential diagnosis somewhat difficult, particularly in sporadic and mosaic cases with multiple schwannomas but without bilateral vestibular schwannomas and detectable germline NF2 gene mutations.

• #20 Schwannomatosis patient who was followed up for fifteen years: A case report

  https://www.wjgnet.com/2307-8960/full/v10/i20/6981.htm

  The pathogenesis of nerve sheath tumor disease is still unclear. The available studies suggest that abnormal expression of the SMARCB1, LZTR1 and NF2 genes is involved in the development of SWNTS. […] The most classic mutation is the „4 strikes and 3 steps” (4-hit/3-step): At first, a germline mutation occurs in the SMARCB1 or LZTR1 gene (the first strike), then a loss of heterozygosity occurs on chromosome 22, resulting in the loss of the second SMARCB1 or LZTR1 allele and the loss of one of the NF2 alleles (the second and third strikes), and finally, there is a somatic mutation of the remaining wild-type NF2 alleles (the fourth strike).

• #21

  https://link.springer.com/article/10.1007/s00439-016-1753-8

  Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and, less commonly, meningiomas. […] Instead, germline mutations of either the SMARCB1 or LZTR1 tumour suppressor genes have been identified in 86% of familial and 40% of sporadic schwannomatosis patients. […] Although biallelic mutations of SMARCB1 or LZTR1 have been detected in the tumours of patients with schwannomatosis, the classical two-hit model of tumorigenesis is insufficient to account for schwannoma growth, since NF2 is also frequently inactivated in these tumours. […] Consequently, tumorigenesis in schwannomatosis must involve the mutation of at least two different tumour suppressor genes, an occurrence frequently mediated by loss of heterozygosity of large parts of chromosome 22q harbouring not only SMARCB1 and LZTR1 but also NF2.

• #22 Schwannomatosis: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/schwannomatosis

  Schwannomatosis is a broad name for several genetic conditions that cause tumors to form on nerves in your body. These tumors are known as schwannomas. […] A genetic variant (mutation) of the NF2, SMARCB1 or LZTR1 gene causes schwannomatosis. These happen on chromosome 22. […] Some cases of schwannomatosis are hereditary. An estimated 15% to 25% of all schwannomatosis diagnoses run in biological families. […] Most cases of schwannomatosis happen randomly, where you do not have a history of the condition in your biological family.

• #23 Schwannomatosis?

  https://www.anausa.org/smf/index.php?topic=4131.0

  Schwannomatosis is a newly recognized neurofibromatosis that is genetically and clinically distinct from NF1 and NF2. Like NF2 it occurs rarely. Inherited forms of the disorder account for only 15 percent of all cases. Researchers still dont fully understand what causes the tumors and the intense pain that are characteristics of the disorder. […] The distinguishing feature of schwannomatosis is the development of multiple schwannomas everywhere in the body except on the vestibular nerve. […] It is seen Schwannomatosis is a Chromosome 22 anomaly also. […] „Does that mean that anybody with AN DOES NOT have schwannomatosis?” Probably so. Anyhow, Schwannomatosis is quite rare. Even more rare than NF-2. Even Drs. don’t have this diagnosed yet.

• #24 Non-NF2-related schwannomatosis

  https://www.genturis.eu/l=eng/thematic-disease-groups/schwannomatosis-and-neurofibromatosis/non-nf2-related-schwannomatosis.html

  Pathogenic variants in SMARCB1, LZTR1 and possibly the DGCR8 genes can cause non NF2-related schwannomatosis. The proteins produced from these genes are thought to act as tumour suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in these genes may help cells grow and divide without control or order to form a tumour. […] Current genetic testing does not reveal a mutation in all affected individuals, and there may be additional genes responsible for the disorder in some people yet to be discovered. […] Studies suggest that 15 to 25 percent of cases of schwannomatosis run in families. These familial cases have an autosomal dominant pattern of inheritance, which means a mutation in one copy of the SMARCB1, LZTR1 or DGCR8 genes in each cell greatly increases the risk of developing schwannomas. However, some people who have an altered gene never develop tumours, which is a situation known as reduced penetrance. […] New alterations occurring in sperm or eggs can end up in every cell of the child and represent approximately 30% for LZTR1-related schwannomatosis and 10% for SMARCB1-related schwannomatosis.

• #25 Schwannomatosis | Neupsy Key

  https://neupsykey.com/schwannomatosis/

  This has led researchers to speculate that loss of some other tumorsuppressor gene, perhaps combined with loss of the NF2 gene, may somehow cause schwannomatosis. […] In light of the conflicting data, some researchers theorize that any one of several different pathological mechanisms may result in schwannomatosis. […] Schwannomatosis is a genetic disorder, but it is not yet clear which gene causes it and how the disorder is inherited. […] Some researchers report that schwannomatosis sometimes skips generations (known medically as incomplete penetrance).

• #26 Non-NF2-related schwannomatosis

  https://www.genturis.eu/l=eng/thematic-disease-groups/schwannomatosis-and-neurofibromatosis/non-nf2-related-schwannomatosis.html

  Pathogenic variants in SMARCB1, LZTR1 and possibly the DGCR8 genes can cause non NF2-related schwannomatosis. The proteins produced from these genes are thought to act as tumour suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in these genes may help cells grow and divide without control or order to form a tumour. […] Current genetic testing does not reveal a mutation in all affected individuals, and there may be additional genes responsible for the disorder in some people yet to be discovered. […] Studies suggest that 15 to 25 percent of cases of schwannomatosis run in families. These familial cases have an autosomal dominant pattern of inheritance, which means a mutation in one copy of the SMARCB1, LZTR1 or DGCR8 genes in each cell greatly increases the risk of developing schwannomas. However, some people who have an altered gene never develop tumours, which is a situation known as reduced penetrance. […] New alterations occurring in sperm or eggs can end up in every cell of the child and represent approximately 30% for LZTR1-related schwannomatosis and 10% for SMARCB1-related schwannomatosis.

• #27 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  On the other hand, missense and in-frame deletions are linked to milder disease courses. […] Similarly, mutations in exons 14 and 15 in the latter parts of the NF2 gene are associated with a milder disease and smaller incidence of meningiomas. […] NF2-related schwannomatosis is inherited in an autosomal dominant disorder with an estimated risk of transmission of 50% to offspring with nearly 100% penetration. […] A significant portion of cases (about 50%) have no prior family history and represent de novo mutations.

• #28 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  NF2-related schwannomatosis is now well characterized clinically as an autosomal dominant disorder with genetic origins on the long arm of chromosome 22. […] NF2-related schwannomatosis is caused by a mutation in the NF2 gene located at chromosome 22q12. NF2-related schwannomatosis is due to inactivation of the neurofibromatosis 2 gene. […] Loss of the second allele is thought to occur in the majority of patients. […] A de novo mutation results in somatic mosaicism, which may hinder a molecular diagnosis unless the specific tumor tissue is examined. Schwannoma growth requires the inactivation of both the two neurofibromatosis 2 alleles. […] This mutation may be a nonsense, a splice-site, or a missense mutation, or it may be a frameshift deletion or insertion. […] Nonsense and frameshift mutations resulting in protein-truncating changes are the most commonly identified germline events and result in the most severe phenotype with a younger age at diagnosis and a higher tumor burden.

• #29

  https://link.springer.com/article/10.1007/s00439-016-1753-8

  Schwannomatosis-associated SMARCB1 mutations are preferentially located either at the 5′ or 3′ end of the gene. […] These findings are suggestive of a genotype/phenotype correlation: loss-of-function mutations occur in patients with rhabdoid tumours, whereas schwannomatosis-associated germline SMARCB1 mutations are predominantly hypomorphic. […] The classical two-hit model of tumorigenesis does not seem to pertain in the tumours of patients with SMARCB1 germline mutations. […] This pattern of mutational events points to a 4-hit/3-step model of tumorigenesis in patients with SMARCB1-positive schwannomatosis. […] Germline SMARCB1 mutations account for 48% of familial and 9.8% of sporadic schwannomatosis cases indicative of probable locus heterogeneity and the existence of additional schwannomatosis predisposition genes.

• #30 Conditioned medium from painful non-NF2 schwannomatosis tumors increases pain behaviors in mice | Scientific Reports

  https://www.nature.com/articles/s41598-025-99820-0

  The majority of non-NF2 schwannomatosis (non-NF2 SWN) patients experience debilitating pain. […] We do not understand the etiology of non-NF2 schwannomatosis related pain. […] It is currently unknown whether mutation status influences the painful phenotype of non-NF2 schwannomatosis, although it has been suggested that patients with mutations in LZTR1 express an increased incidence of pain. […] Due to the heterogeneity of the painful phenotype seen between and within non-NF2 schwannomatosis patients, we speculate that there is an alteration occurring in the schwannoma itself and that this alters the behavior of nociceptive neurons. […] Our study demonstrates definitive differences in levels of cytokines secreted by painful and non-painful tumors and significant effects on neuronal sensitization in vitro.

• #31

  https://link.springer.com/article/10.1007/s00439-016-1753-8

  Schwannomatosis-associated SMARCB1 mutations are preferentially located either at the 5′ or 3′ end of the gene. […] These findings are suggestive of a genotype/phenotype correlation: loss-of-function mutations occur in patients with rhabdoid tumours, whereas schwannomatosis-associated germline SMARCB1 mutations are predominantly hypomorphic. […] The classical two-hit model of tumorigenesis does not seem to pertain in the tumours of patients with SMARCB1 germline mutations. […] This pattern of mutational events points to a 4-hit/3-step model of tumorigenesis in patients with SMARCB1-positive schwannomatosis. […] Germline SMARCB1 mutations account for 48% of familial and 9.8% of sporadic schwannomatosis cases indicative of probable locus heterogeneity and the existence of additional schwannomatosis predisposition genes.

• #32 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  NF2-related schwannomatosis is now well characterized clinically as an autosomal dominant disorder with genetic origins on the long arm of chromosome 22. […] NF2-related schwannomatosis is caused by a mutation in the NF2 gene located at chromosome 22q12. NF2-related schwannomatosis is due to inactivation of the neurofibromatosis 2 gene. […] Loss of the second allele is thought to occur in the majority of patients. […] A de novo mutation results in somatic mosaicism, which may hinder a molecular diagnosis unless the specific tumor tissue is examined. Schwannoma growth requires the inactivation of both the two neurofibromatosis 2 alleles. […] This mutation may be a nonsense, a splice-site, or a missense mutation, or it may be a frameshift deletion or insertion. […] Nonsense and frameshift mutations resulting in protein-truncating changes are the most commonly identified germline events and result in the most severe phenotype with a younger age at diagnosis and a higher tumor burden.

• #33 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  On the other hand, missense and in-frame deletions are linked to milder disease courses. […] Similarly, mutations in exons 14 and 15 in the latter parts of the NF2 gene are associated with a milder disease and smaller incidence of meningiomas. […] NF2-related schwannomatosis is inherited in an autosomal dominant disorder with an estimated risk of transmission of 50% to offspring with nearly 100% penetration. […] A significant portion of cases (about 50%) have no prior family history and represent de novo mutations.

• #34 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  On the other hand, missense and in-frame deletions are linked to milder disease courses. […] Similarly, mutations in exons 14 and 15 in the latter parts of the NF2 gene are associated with a milder disease and smaller incidence of meningiomas. […] NF2-related schwannomatosis is inherited in an autosomal dominant disorder with an estimated risk of transmission of 50% to offspring with nearly 100% penetration. […] A significant portion of cases (about 50%) have no prior family history and represent de novo mutations.

• #35 Schwannomatosis | About the Disease | GARD

  https://rarediseases.info.nih.gov/diseases/4768/schwannomatosis

  Schwannomatosis is caused by changes in the SMARCB1 or LZTR1 genes; in other cases, the exact underlying cause is unknown. […] This disease is caused by a change in the genetic material (DNA). […] Schwannomatosis is caused by genetic mutations, also known as pathogenic variants. […] Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these. […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.

• #36 NF2-related schwannomatosis | MedLink Neurology

  https://www.medlink.com/articles/nf2-related-schwannomatosis

  NF2-related schwannomatosis is now well characterized clinically as an autosomal dominant disorder with genetic origins on the long arm of chromosome 22. […] NF2-related schwannomatosis is caused by a mutation in the NF2 gene located at chromosome 22q12. NF2-related schwannomatosis is due to inactivation of the neurofibromatosis 2 gene. […] Loss of the second allele is thought to occur in the majority of patients. […] A de novo mutation results in somatic mosaicism, which may hinder a molecular diagnosis unless the specific tumor tissue is examined. Schwannoma growth requires the inactivation of both the two neurofibromatosis 2 alleles. […] This mutation may be a nonsense, a splice-site, or a missense mutation, or it may be a frameshift deletion or insertion. […] Nonsense and frameshift mutations resulting in protein-truncating changes are the most commonly identified germline events and result in the most severe phenotype with a younger age at diagnosis and a higher tumor burden.

• #37 Schwannomatosis | About the Disease | GARD

  https://rarediseases.info.nih.gov/diseases/4768/schwannomatosis

  Schwannomatosis is caused by changes in the SMARCB1 or LZTR1 genes; in other cases, the exact underlying cause is unknown. […] This disease is caused by a change in the genetic material (DNA). […] Schwannomatosis is caused by genetic mutations, also known as pathogenic variants. […] Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these. […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.

• #38 Schwannomatosis | About the Disease | GARD

  https://rarediseases.info.nih.gov/diseases/4768/schwannomatosis

  Schwannomatosis is caused by changes in the SMARCB1 or LZTR1 genes; in other cases, the exact underlying cause is unknown. […] This disease is caused by a change in the genetic material (DNA). […] Schwannomatosis is caused by genetic mutations, also known as pathogenic variants. […] Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these. […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.

• #39 Conditioned medium from painful non-NF2 schwannomatosis tumors increases pain behaviors in mice | Scientific Reports

  https://www.nature.com/articles/s41598-025-99820-0

  The majority of non-NF2 schwannomatosis (non-NF2 SWN) patients experience debilitating pain. […] We do not understand the etiology of non-NF2 schwannomatosis related pain. […] It is currently unknown whether mutation status influences the painful phenotype of non-NF2 schwannomatosis, although it has been suggested that patients with mutations in LZTR1 express an increased incidence of pain. […] Due to the heterogeneity of the painful phenotype seen between and within non-NF2 schwannomatosis patients, we speculate that there is an alteration occurring in the schwannoma itself and that this alters the behavior of nociceptive neurons. […] Our study demonstrates definitive differences in levels of cytokines secreted by painful and non-painful tumors and significant effects on neuronal sensitization in vitro.

• #40 Conditioned medium from painful non-NF2 schwannomatosis tumors increases pain behaviors in mice | Scientific Reports

  https://www.nature.com/articles/s41598-025-99820-0

  These data, derived using an expanded cohort of painful and non-painful CM, validate our previous in vitro results. Additional testing of painful CM in vivo may lead to a better understanding of the etiology of SWN-related pain and guide the rational development of personalized therapies for pain in patients suffering from these disorders.

• #41 Schwannomatosis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/schwannomatosis?lang=us

  Schwannomatosis, also known as neurilemmomatosis, is a condition characterized by multiple schwannomas, and occasionally meningiomas, but without meeting criteria for neurofibromatosis type 2 (NF2). Some consider this as a variant of NF2, but this article considers schwannomatosis an independent disease. […] The combined clinical and molecular diagnosis of schwannomatosis requires either of the following: at least 2 pathologically confirmed schwannomas or meningiomas with chromosome 22q loss of heterozygosity and 2 different somatic NF2 mutations […] Patients are excluded if they have a germline pathogenic NF2 mutation. […] The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis.

• #42 Schwannomatosis – Children’s Tumor Foundation

  https://www.ctf.org/swn/

  Genetic testing for the genes known to be involved in all types of schwannomatosis is available and should be completed whenever possible for a patient suspected of SWN. Testing is required to diagnose a specific type of schwannomatosis, except NF2-related schwannomatosis, which does not require genetic testing if clinical criteria are met.

• #43 Schwannomatosis – Children’s Tumor Foundation

  https://www.ctf.org/swn/

  Genetic testing for the genes known to be involved in all types of schwannomatosis is available and should be completed whenever possible for a patient suspected of SWN. Testing is required to diagnose a specific type of schwannomatosis, except NF2-related schwannomatosis, which does not require genetic testing if clinical criteria are met.

• #44 La schwannomatose

  https://www.genturis.eu/l=fra/syndromes/neurofibromatoses/la-schwannomatose.html

  Mutations in SMARCB1 and LZTR1 can cause schwannomatosis. The proteins produced from both genes are thought to act as tumour suppressors, which normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in either of these genes may help cells grow and divide without control or order to form a tumour. SMARCB1 and LZTR1 are located on chromosome 22q, near the NF2 gene. […] Current genetic testing does not reveal a mutation in all affected individuals, and there may be additional genes responsible for the disorder in some people yet to be discovered.

• #45 Schwannomatosis – Tumour Foundation of BC

  https://www.tumourfoundation.ca/schwannomatosis/

  Because of the small number of people that have been diagnosed with schwannomatosis, and because of the little amount of information that doctors have about what causes this condition and how to treat it, the International Schwannomatosis Database (ISD) project is proposing to bring together people with this diagnosis and people studying and managing this condition around the world.

• #46

  http://sid2011.squarespace.com/

  Schwannomatosis is a genetic condition, but the complete genetic mechanism of this condition is not well understood at this time. […] because of the little amount of information that doctors have about what causes this condition and how to treat it, the International Schwannomatosis Database project is proposing to bring together people with this diagnosis and people studying and managing this condition around the world so that we might better understand the schwannomatosis and how best to treat it.

• #47 Screening Trial for Pain Relief in Schwannomatosis, STARFISH Trial – NCIFacebookFollow on XInstagramYoutubeLinkedin

  https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2023-06932

  This phase II STARFISH screening and multi-sub study trial is being done to test the safety, pain responses, and pharmacodynamic activity of multiple experimental therapies simultaneously in patients with schwannomatosis (SWN) and moderate-to-severe pain. […] The etiology of pain in SWN remains poorly understood, and there are no effective therapies that relieve SWN-related pain. […] Therefore, developing a platform to study tumor-induced pain and identify novel strategies that relieve pain in patients with SWN is a significant unmet need.

• #48 STARS

  https://stars.library.ucf.edu/honorstheses/665/

  Schwannomatosis is a rare genetic disorder that causes development of benign schwannomas in nerves, and intractable chronic pain. Mutations in two genes, SMARCB1 and LZTR1 are found in a subset of patients while the underlying cause remains unknown for the majority. […] The results of this study suggest CPD X may be a therapeutic compound for schwannomatosis related tumors and justifies further study in an in-vivo model.

• #49

  https://link.springer.com/article/10.1007/s00439-016-1753-8

  Piotrowski et al. (2014) identified LZTR1 germline mutations in 16 of 20 unrelated schwannomatosis patients (80%). […] These findings suggest that LZTR1 mutations do not predispose to meningiomas. […] The comprehensive genome-wide analysis of the mutational landscape of somatic mutations in schwannomas of patients with schwannomatosis has not so far been performed but would improve our understanding of the tumorigenic process in schwannomatosis.

• #50 Schwannomatosis – Children’s Tumor Foundation

  https://www.ctf.org/swn/

  Schwannomatosis is a type of NF in which individuals develop tumors, called schwannomas, on nerves in the central nervous system (brain and spine) and on peripheral nerves, which are the nerves throughout the rest of the body. Schwannomas are benign, meaning they are not cancer. These tumors can affect patients in many ways, such as hearing loss, eye problems, or pain that may be hard to manage. […] There are at least three genes, NF2, LZTR1, and SMARCB1 that are known to cause schwannomatosis, and there may be additional genes discovered in the future. These genes are thought to help regulate cell growth and division. If these genes are not functioning properly, the cells may multiply excessively and form tumors. […] All types of schwannomatosis are a result of a change in a gene (a sequence of DNA) located on chromosome 22. When a gene changes in a way that keeps it from working correctly, it is called a pathogenic variant (formerly called a gene mutation). Therefore, the different types of SWN are named by identifying the pathogenic variant that is the cause of the diagnosis, like so: GENE-related schwannomatosis (gene names are in italics).

• #51 NF2 – SWN | ANFQ

  https://anfq.ca/en/nf2-swn/

  SWN is a genetic disease caused by pathogenic variants of a gene located on chromosome 22. […] There are at least three genes, NF2, LZTR1 and SMARCB1, known to cause schwannomatosis, and more genes may be discovered in the future. […] NF2-related schwannomatosis (NF2-SWN), otherwise known as neurofibromatosis type 2, is a genetic disease caused by pathogenic variants of a gene located on chromosome 22. […] Like NF1, NF2 schwannomatosis is inherited from one parent in half of all cases. […] In the other half of patients, NF2-related schwannomatosis occurs without a parent: in this case, the sufferer is said to have contracted the genetic disorder through spontaneous mutation. […] Whats important to know is that people with this type of NF, whether they inherited it from a parent or contracted it through spontaneous mutation, have a 50% chance of passing the disorder on to each of their children.

• #52 Screening Trial for Pain Relief in Schwannomatosis, STARFISH Trial – NCIFacebookFollow on XInstagramYoutubeLinkedin

  https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2023-06932

  This phase II STARFISH screening and multi-sub study trial is being done to test the safety, pain responses, and pharmacodynamic activity of multiple experimental therapies simultaneously in patients with schwannomatosis (SWN) and moderate-to-severe pain. […] The etiology of pain in SWN remains poorly understood, and there are no effective therapies that relieve SWN-related pain. […] Therefore, developing a platform to study tumor-induced pain and identify novel strategies that relieve pain in patients with SWN is a significant unmet need.

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