Materiały źródłowe

• #1 Neurofibromatosis Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470350/

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors involving the central nervous system (CNS). […] The clinical diagnosis of NF2 is based on the presence of any 1 of the following criteria: […] Detailed clinical and family histories are required from the patients suspected of having NF2. A complete physical examination should be done to look for cutaneous schwannomas or plaque-like lesions, and an ophthalmic examination should be done to look for cataracts and optic nerve, among other things. […] For tumor surveillance, an annual brain MRI is recommended. If no brain tumor is seen on the initial imaging, then MRI can be done every 2 years. If the tumor is seen, an MRI should be done twice in the first year, followed by an annual follow-up. […] Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is a new systemic immunotherapy for many tumors. Some studies have shown tumor regression and hearing improvement in NF2 patients treated with bevacizumab.

• #2 Neurofibromatosis Type 2 Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/neurofibromatosis-type-2

  Neurofibromatosis type 2 (NF2) is a rare genetic condition characterized by tumors in the peripheral and central nervous system. […] Imaging studies are required to detect acoustic neuromas, or other tumors, and in turn diagnose NF2. Either computed tomography (CT) scans or magnetic resonance imaging (MRI) scans can be conducted to visualize any tumors; however, the preferred test is MRI. […] A tissue biopsy is needed to confirm the type of tumor. […] Also, a blood sample may be obtained for genetic testing to identify a possible NF2 mutation.

• #3 Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35674741/

• #4 Diagnostic Criteria Update – Children’s Tumor Foundation

  https://www.ctf.org/diagnostic-criteria/

  In 2022, an update to the diagnostic criteria for the genetic disorders formerly referred to as neurofibromatosis type two (NF2) and schwannomatosis was published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG). […] The updated diagnostic criteria for schwannomatosis classify each disorder according to the specific gene harboring a pathogenic variant (formerly called a gene mutation). Therefore, NF2 is now termed NF2-related schwannomatosis. […] There has been some confusion and overlap in the diagnosis of all types of neurofibromatosis and schwannomatosis, and the updated criteria intend to improve patient care by reducing misdiagnosis.

• #5 Genetic Testing for Neurofibromatosis and Related Disorders

  https://www.southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/genetic-testing-for-neurofibromatosis-and-related-disorders/

  Updated diagnostic criteria for NF2-related schwannomatosis: A diagnosis of NF2-related schwannomatosis (previously termed neurofibromatosis 2, NF2) can be made when an individual has one of the following: 1. Bilateral vestibular schwannomas (VS) 2. An identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma). […] Diagnostic criteria for SMARCB1- and LZTR1-related schwannomatosis can be made when an individual meets 1 of the following criteria: At least 1 pathologically confirmed schwannoma or hybrid nerve sheath tumor and a SMARCB1 (or LZTR1) pathogenic variant in an unaffected tissue such as blood. […] A shared SMARCB1 or LZTR1 pathogenic variant in 2 schwannomas or hybrid nerve sheath tumors (Plotkin et al., 2022).

• #6 Neurofibromatosis Type 2: Causes, Diagnosis, Treatment

  https://www.verywellhealth.com/neurofibromatosis-type-2-nf2-2860838

  Neurofibromatosis type 2 (NF2) can be diagnosed with brain imaging studies and a physical exam. […] The diagnostic criteria for neurofibromatosis type 2 changed in 2022. […] MRI is highly sensitive and can readily detect schwannomas, meningiomas, and gliomas. […] The person needs to have one of the following: Bilateral vestibular schwannomas (VS), meaning schwannomas in both ears; NF2 pathogenic gene variants in at least two different NF2-related tumors (schwannoma, meningioma, and/or ependymoma); Either two major or one major and two minor other criteria. […] Since hearing loss is characteristic of NF2, a hearing test (audiometry) would be performed. […] Genetic testing for mutations in the NF2 gene is available for people diagnosed with NF2. […] The diagnosis of NF2 is based largely on a physical exam and MRI.

• #7 NF Criteria

  https://www.nf2is.org/nf-criteria.php

  The 2018 revision of diagnosis for neurofibromatosis type 2 (NF2) change the tumor type of glioma, to ependymoma, and remove of neurofibroma. […] NF2 Diagnostic Criteria as of 2018 (December 2018 – now) […] Confirmed (Definite) Diagnosis […] Presumed (Probable) Diagnosis […] Bilateral Vestibular Schwannoma […] Unilateral Vestibular Schwannoma, or Any two (2) other NF2-Associated lesions: Meningioma, Schwannoma, Ependymoma, or Juvenile Cataracts […] Unilateral Vestibular Schwannoma Any two (2) other NF2-Associated lesions: Meningioma, Schwannoma, Ependymoma, or Juvenile Cataract […] Multiple Meningiomas Unilateral Vestibular Schwannoma, or Any two (2) other NF2-Associated lesions: Schwannoma, Ependymoma, or Juvenile Cataracts.

• #8 Neurofibromatosis: Type 2 | PM&R KnowledgeNow

  https://now.aapmr.org/neurofibromatosis-type-2/

  Patients suspected of having NF2 should undergo comprehensive assessments, including skin evaluation for neurofibromas, ophthalmoscopic exams for ocular issues, full neurological exams to check cranial nerves, reflexes, and coordination, and musculoskeletal evaluations to detect changes in muscle tone and strength. Diagnosis now emphasizes comprehensive molecular genetic testing due to the phenotypic overlap of NF2 and SWN, moving beyond the primarily clinical-based Manchester criteria. […] A diagnosis of NF2-related schwannomatosis is confirmed if an individual has bilateral vestibular schwannomas or an identical NF2 pathogenic variant in at least two anatomically distinct tumors like schwannoma, meningioma, or ependymoma. If the variant allele fraction (VAF) in unaffected tissues is under 50%, the condition is classified as mosaic. Diagnosis may also be based on criteria combinations: either two major, or one major and two minor, with major criteria including unilateral vestibular schwannomas, having a first-degree relative with NF2-related schwannomatosis, or two or more meningiomas, and minor criteria such as multiple distinct schwannomas, ependymomas, or juvenile ocular abnormalities.

• #9 Empirical development of improved diagnostic criteria for neurofibromatosis 2 | Genetics in Medicine

  https://www.nature.com/articles/gim9201192

  Purpose: Four sets of clinical diagnostic criteria have been proposed for neurofibromatosis 2, but all have low sensitivity at the time of initial clinical assessment for the disease among patients with a negative family history who do not present with bilateral vestibular schwannomas. […] We have empirically developed and tested an improved set of diagnostic criteria that uses current understanding of the natural history and genetic characteristics of neurofibromatosis 2 to increase sensitivity while maintaining very high specificity. […] On the basis of this analysis, we developed the Baser criteria, a new diagnostic system that incorporates genetic testing and gives more weight to the most characteristic features and to those that occur before 30 years of age. […] In an independent validation subset of patients with unequivocal neurofibromatosis 2, the Baser criteria increased diagnostic sensitivity to 79% (915% greater than previous sets of criteria) while maintaining 100% specificity at the age at onset of the first characteristic sign of neurofibromatosis 2.

• #10 Empirical development of improved diagnostic criteria for neurofibromatosis 2 | Genetics in Medicine

  https://www.nature.com/articles/gim9201192

  The Baser criteria permit early diagnosis in a greater proportion of patients with neurofibromatosis 2 than previous sets of diagnostic criteria. […] By taking into account the clinical availability of high-quality MRI and molecular genetic testing and by incorporating new knowledge about somatic mosaicism and the natural history of NF2, these new criteria provide increased sensitivity while maintaining very high specificity. […] The Baser criteria’s explicit consideration of molecular genetic testing results is especially valuable for younger patients, who often do not present with bilateral VS, and for older patients, in whom knowledge of when various features developed is unavailable. […] A diagnosis of definite NF2 is established if the number of points exceeds 6. A score of 4 or more points is considered to be an indication to do NF2 molecular testing, and definite NF2 may also be diagnosed if the patient is found to have a constitutional pathogenic mutation of the NF2 gene in the blood.

• #11 Neurofibromatosis Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470350/

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors involving the central nervous system (CNS). […] The clinical diagnosis of NF2 is based on the presence of any 1 of the following criteria: […] Detailed clinical and family histories are required from the patients suspected of having NF2. A complete physical examination should be done to look for cutaneous schwannomas or plaque-like lesions, and an ophthalmic examination should be done to look for cataracts and optic nerve, among other things. […] For tumor surveillance, an annual brain MRI is recommended. If no brain tumor is seen on the initial imaging, then MRI can be done every 2 years. If the tumor is seen, an MRI should be done twice in the first year, followed by an annual follow-up. […] Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is a new systemic immunotherapy for many tumors. Some studies have shown tumor regression and hearing improvement in NF2 patients treated with bevacizumab.

• #12 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  How is NF2-related schwannomatosis (neurofibromatosis type 2) diagnosed? A healthcare provider will diagnose NF2-related schwannomatosis (neurofibromatosis type 2) after a physical exam and testing. During the exam, theyll look for signs of the condition, learn more about your family medical history and ask questions about your symptoms. Imaging tests like an MRI can help them find tumors in your nervous system and skin. Other tests may include: A hearing test. An eye exam. Genetic testing. […] While there isnt currently a cure for neurofibromatosis type 2, there have been multiple advances in diagnosing and treating NF2-related tumors. Your healthcare provider can direct you toward the best treatment available for your condition. Treatment could include: Surgery to remove tumors or treat cataracts. Chemotherapy or radiation therapy like stereotactic radiotherapy to reduce the size of tumors. Hearing aids, cochlear implants, an auditory brainstem implant for hearing preservation. Assistive devices for vision loss like glasses. Mobility devices for symptoms that affect your nerves and movement. Medications to manage symptoms like pain.

• #13 79 Diagnosis and Evaluation of Neurofibromatosis Type 2 | Neupsy Key

  https://neupsykey.com/79-diagnosis-and-evaluation-of-neurofibromatosis-type-2/

  Neurofibromatosis type 2 (NF2) is a rare neurogenetic syndrome inherited in an autosomal dominant pattern, with an estimated incidence of roughly 1:30,000. The diagnosis of NF2 can be made on the basis of either clinical or molecular evidence. Patients with an established family history of NF2 are often identified early in the course of disease from screening protocols or heightened suspicion. […] In contrast, an early clinical diagnosis of NF2 in patients without a family history of the disease can be challenging, as the presenting signs and symptoms are frequently nonspecific. […] Although the constellation of multiple schwannomas and meningiomas is a hallmark of NF2, some patients may initially present with only one or two tumors findings that may not directly suggest NF2 or reach diagnostic criteria at initial presentation.

• #14 Neurofibromatosis Type 2 Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/neurofibromatosis-type-2

  Neurofibromatosis type 2 (NF2) is a rare genetic condition characterized by tumors in the peripheral and central nervous system. […] Imaging studies are required to detect acoustic neuromas, or other tumors, and in turn diagnose NF2. Either computed tomography (CT) scans or magnetic resonance imaging (MRI) scans can be conducted to visualize any tumors; however, the preferred test is MRI. […] A tissue biopsy is needed to confirm the type of tumor. […] Also, a blood sample may be obtained for genetic testing to identify a possible NF2 mutation.

• #15 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  Diagnosis of NF2 involves the following: Genetic testing, Imaging studies, Auditory, ophthalmic, and histologic examinations. […] Once the clinical diagnosis has been established in a given individual, direct molecular analysis can be offered. […] Detection rates for molecular-based testing approaches approaches 72% in simplex cases and 93% in familial cases. […] If a mutation is found, other asymptomatic family members might benefit from presymptomatic testing. […] Molecular testing of tumor tissue may augment traditional molecular studies when analysis of DNA obtained from blood lymphocytes is nondiagnostic. […] MRI remains the mainstay for diagnosis and screening of CNS, cranial nerve, and spinal cord tumors. […] At-risk individuals may be monitored for CNS tumors beginning in their teens, with annual MRI scans of the head performed through their late 50s.

• #16 Neurofibromatosis Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470350/

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors involving the central nervous system (CNS). […] The clinical diagnosis of NF2 is based on the presence of any 1 of the following criteria: […] Detailed clinical and family histories are required from the patients suspected of having NF2. A complete physical examination should be done to look for cutaneous schwannomas or plaque-like lesions, and an ophthalmic examination should be done to look for cataracts and optic nerve, among other things. […] For tumor surveillance, an annual brain MRI is recommended. If no brain tumor is seen on the initial imaging, then MRI can be done every 2 years. If the tumor is seen, an MRI should be done twice in the first year, followed by an annual follow-up. […] Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is a new systemic immunotherapy for many tumors. Some studies have shown tumor regression and hearing improvement in NF2 patients treated with bevacizumab.

• #17 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  MRI using 3-dimensional (3D) volumetrics is now the preferred method for following vestibular schwannoma growth over time. […] Hearing evaluations, including brainstem auditory-evoked response (BAER) may demonstrate latency abnormalities before a mass is detectable on MRI. […] Annual eye examinations are recommended for children and adults with NF2. […] Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression. […] Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations. […] Annual MRI to monitor existing lesions or look for presymptomatic lesions. […] Annual ophthalmologic evaluations to monitor visual acuity.

• #18 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  MRI using 3-dimensional (3D) volumetrics is now the preferred method for following vestibular schwannoma growth over time. […] Hearing evaluations, including brainstem auditory-evoked response (BAER) may demonstrate latency abnormalities before a mass is detectable on MRI. […] Annual eye examinations are recommended for children and adults with NF2. […] Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression. […] Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations. […] Annual MRI to monitor existing lesions or look for presymptomatic lesions. […] Annual ophthalmologic evaluations to monitor visual acuity.

• #19 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  How is NF2-related schwannomatosis (neurofibromatosis type 2) diagnosed? A healthcare provider will diagnose NF2-related schwannomatosis (neurofibromatosis type 2) after a physical exam and testing. During the exam, theyll look for signs of the condition, learn more about your family medical history and ask questions about your symptoms. Imaging tests like an MRI can help them find tumors in your nervous system and skin. Other tests may include: A hearing test. An eye exam. Genetic testing. […] While there isnt currently a cure for neurofibromatosis type 2, there have been multiple advances in diagnosing and treating NF2-related tumors. Your healthcare provider can direct you toward the best treatment available for your condition. Treatment could include: Surgery to remove tumors or treat cataracts. Chemotherapy or radiation therapy like stereotactic radiotherapy to reduce the size of tumors. Hearing aids, cochlear implants, an auditory brainstem implant for hearing preservation. Assistive devices for vision loss like glasses. Mobility devices for symptoms that affect your nerves and movement. Medications to manage symptoms like pain.

• #20 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  MRI using 3-dimensional (3D) volumetrics is now the preferred method for following vestibular schwannoma growth over time. […] Hearing evaluations, including brainstem auditory-evoked response (BAER) may demonstrate latency abnormalities before a mass is detectable on MRI. […] Annual eye examinations are recommended for children and adults with NF2. […] Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression. […] Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations. […] Annual MRI to monitor existing lesions or look for presymptomatic lesions. […] Annual ophthalmologic evaluations to monitor visual acuity.

• #21 Neurofibromatosis: Type 2 | PM&R KnowledgeNow

  https://now.aapmr.org/neurofibromatosis-type-2/

  Genetic testing identifies abnormalities of the NF2 gene on chromosome 22, altering expression of the tumor suppressor merlin. Frame shift and missense mutations are most common in familial cases. […] Contrast-enhanced MRI of the brain or spinal cord is often required to appropriately characterize tumors before resection. Additional neuroimaging may be necessary if other focal neurologic signs or symptoms are observed. […] Patients need an annual hearing assessment, potentially including brainstem auditory evoked responses, to check for early signs of schwannoma recurrence before other symptoms appear. Preoperative audiologic tests can inform surgical strategies to minimize complications and aid in preserving hearing. Regular yearly examinations by an ophthalmologist and dermatologist are necessary to track disease progression. Starting between the ages of 10 and 12, craniospinal MRI should be conducted every two years for individuals under 20, and every three to five years afterward. If tumors are identified, imaging should be carried out annually.

• #22 Neurofibromatosis Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470350/

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors involving the central nervous system (CNS). […] The clinical diagnosis of NF2 is based on the presence of any 1 of the following criteria: […] Detailed clinical and family histories are required from the patients suspected of having NF2. A complete physical examination should be done to look for cutaneous schwannomas or plaque-like lesions, and an ophthalmic examination should be done to look for cataracts and optic nerve, among other things. […] For tumor surveillance, an annual brain MRI is recommended. If no brain tumor is seen on the initial imaging, then MRI can be done every 2 years. If the tumor is seen, an MRI should be done twice in the first year, followed by an annual follow-up. […] Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is a new systemic immunotherapy for many tumors. Some studies have shown tumor regression and hearing improvement in NF2 patients treated with bevacizumab.

• #23 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  MRI using 3-dimensional (3D) volumetrics is now the preferred method for following vestibular schwannoma growth over time. […] Hearing evaluations, including brainstem auditory-evoked response (BAER) may demonstrate latency abnormalities before a mass is detectable on MRI. […] Annual eye examinations are recommended for children and adults with NF2. […] Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression. […] Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations. […] Annual MRI to monitor existing lesions or look for presymptomatic lesions. […] Annual ophthalmologic evaluations to monitor visual acuity.

• #24 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  MRI using 3-dimensional (3D) volumetrics is now the preferred method for following vestibular schwannoma growth over time. […] Hearing evaluations, including brainstem auditory-evoked response (BAER) may demonstrate latency abnormalities before a mass is detectable on MRI. […] Annual eye examinations are recommended for children and adults with NF2. […] Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression. […] Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations. […] Annual MRI to monitor existing lesions or look for presymptomatic lesions. […] Annual ophthalmologic evaluations to monitor visual acuity.

• #25 Neurofibromatosis Type 2 Workup: Approach Considerations, Genetic Studies, Imaging Studies

  https://emedicine.medscape.com/article/1178283-workup

  Genetic analysis for disease-causing mutations of neurofibromatosis type 2 (NF2) is clinically available. Detection rates for molecular-based testing approaches 72% in simplex cases; therefore, such testing has some inherent limitations when trying to confirm a diagnosis of NF2. However, for a patient with suspected NF2 who is still young, has a negative family history, and may eventually develop additional criteria, the identification of a specific mutation may be very helpful. […] Imaging studies and auditory, ophthalmic, and histologic examinations are also important in the diagnosis and management of NF2. […] MRI remains the mainstay for diagnosis and screening of CNS, cranial nerve, and spinal cord tumors. At-risk individuals may be monitored for CNS tumors beginning in their teens, with annual MRI scans of the head performed through their late 50s.

• #26 Neurofibromatosis Type 2 | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/genetic-syndromes/neurofibromatosis-type-2.html

  A health care provider may suspect that your child has NF2 after studying their medical and family cancer history. This information helps the health care provider and the genetic counselor know if: […] If your doctor or genetic counselor may recommend genetic testing if they suspect NF2. […] A blood sample is sent to a genetic testing lab. The lab will run a special type of genetic test, called next generation sequencing that looks for changes in the NF2 gene. […] Genetic testing can detect a mutated NF2 gene in about 90-95% of people with a clinical diagnosis of NF2 and no family history of the condition. […] A diagnosis of NF2 can be made with or without genetic testing. Genetic testing can be offered to people who have signs and symptoms of NF2 to confirm the diagnosis.

• #27 Neurofibromatosis Type 2 | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/neurofibromatosis-type-2

  If an individual meets the diagnostic criteria for NF2, the doctor might also use genetic testing to confirm the diagnosis. However, these tests often aren’t necessary to confirm a diagnosis. […] If a parent has NF2 and a known mutation, genetic testing can be performed to determine if the baby has inherited the same mutation. […] The age at which a given person is diagnosed with NF2 varies depends on the individual. The average age for diagnosis is 28 years. However, more severe cases of the disorder will be detected earlier than in individuals who show milder symptoms. In familial cases of NF2, if the parental mutation is known, the child can be tested at any age.

• #28 NF2 – genetic testing

  https://www.eviq.org.au/cancer-genetics/adult/genetic-testing-for-heritable-pathogenic-variants/1909-nf2-genetic-testing

  Individual meeting clinical criteria for NF2 according to revised Manchester criteria for NF2 […] The decision to offer a genetic test should be based on the pre-test probability of identifying a heritable pathogenic variant, the performance of the test (e.g. false negative rate) and the patient’s choice. […] Due to a high level of somatic mosaicism, NF2 pathogenic variant search and loss of heterozygosity (LOH) testing in tumour tissue is recommended. […] The frequency of heritable pathogenic variants in the NF2 gene is 72% in isolated individuals (simplex cases) meeting NF2 diagnostic criteria and 91% in familial cases. […] Genetic testing is not indicated in the following circumstances: individuals with an isolated NF2-related tumour (excluding vestibular schwannoma) diagnosed over age 20 years and with no family history of NF2.

• #29 Neurofibromatosis type 2 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/neurofibromatosis-type-2

  For an individual with no known family history of neurofibromatosis type 2, the occurrence of one or more of the following features confirms a diagnosis of the condition: […] For an individual with a positive family history of neurofibromatosis type 2, a clinical diagnosis is established by the presence of any one of the following: […] A detailed review of an individuals medical and family history is important in diagnosing neurofibromatosis type 2. […] If the pattern of clinical features is suggestive of neurofibromatosis type 2, the physician or counselor may recommend that genetic testing be performed. […] In order to confirm on a molecular level that an individual has neurofibromatosis type 2, he or she can undergo genetic testing: […] It is estimated that about 93 percent of individuals with familial neurofibromatosis type 2 will have a mutation involving NF2. […] In patients with no family history of neurofibromatosis type 2, the mutation detection rate drops to 60 to 75 percent. […] Therefore, the failure to identify an alteration in the NF2 gene does not exclude a clinical diagnosis of neurofibromatosis type 2.

• #30 NF2 – genetic testing

  https://www.eviq.org.au/cancer-genetics/adult/genetic-testing-for-heritable-pathogenic-variants/1909-nf2-genetic-testing

  A variant-specific test (rather than sequencing a single gene or gene panel) may be more cost effective and appropriate where: a known pathogenic variant has been identified in a relative. […] A range of testing methodologies are needed to identify pathogenic changes in the NF2 gene including: tumour sequencing and loss of heterozygosity (LOH), next generation sequencing, copy number analysis (e.g. MLPA, high-resolution microarray). […] If a pathogenic variant is identified refer to a clinical genetics service or familial cancer centre for review, family risk notification and predictive testing.

• #31 Orphanet: Diagnosis of neurofibromatosis type II (NF2 gene)

  https://www.orpha.net/en/diagnostic-tests/diagnostic/73543?country=&name=&mode=

  Diagnosis of neurofibromatosis type II (NF2 gene) […] Post-natal diagnosis […] Technical procedure(s) Molecular genetics Sequence analysis: entire coding region Sanger sequencing Deletion / Duplication analysis MLPA based techniques […] List of diseases and genes List of diseases tested (1) Full NF2-related schwannomatosis […] List of genes tested (1) NF2.

• #32 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  Diagnosis of NF2 involves the following: Genetic testing, Imaging studies, Auditory, ophthalmic, and histologic examinations. […] Once the clinical diagnosis has been established in a given individual, direct molecular analysis can be offered. […] Detection rates for molecular-based testing approaches approaches 72% in simplex cases and 93% in familial cases. […] If a mutation is found, other asymptomatic family members might benefit from presymptomatic testing. […] Molecular testing of tumor tissue may augment traditional molecular studies when analysis of DNA obtained from blood lymphocytes is nondiagnostic. […] MRI remains the mainstay for diagnosis and screening of CNS, cranial nerve, and spinal cord tumors. […] At-risk individuals may be monitored for CNS tumors beginning in their teens, with annual MRI scans of the head performed through their late 50s.

• #33 Genetic Testing for Neurofibromatosis and Related Disorders AHS – M2134 | Providers | Blue Cross NC

  https://www.bluecrossnc.com/providers/policies-guidelines-codes/commercial/laboratory/updates/genetic-testing-for-neurofibromatosis-and-related-disorders

  Clinical criteria for NF2 were initially established with those for NF1 and they were modified as the Manchester criteria to include molecular diagnostics and increase specificity without affecting sensitivity. Most recently, the identification of LZTR1 as a cause of schwannomatosis reduces the specificity of these more inclusive criteria and even the presence of bilateral VS is now no longer sufficient to be certain that an individual has NF2, resulting in further modification of the Manchester criteria. […] Detailed molecular testing is reported to identify mutations in NF2 in 93% of families with multiple members affected by NF2. Early diagnosis of individuals with NF2 facilitates treatment and reduction of mortality; however, genetic testing and management is complicated by the well-documented risk of mosaicism. More so than with NF1, the stronger genotype/phenotype correlations in mutations of NF2, high frequency of de novo mutations, and presentation of patients before clinical diagnostic criteria are fulfilled have provided a stronger rationale for the clinical utility of molecular testing than for NF1.

• #34 Neurofibromatosis type 2 (NF2): A clinical and molecular review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-16

  Neurofibromatosis type 2 (NF2) is a dominantly inherited tumour prone disorder characterised by the development of multiple schwannomas and meningiomas. […] Diagnosis is based on clinical and neuroimaging studies. […] The Manchester (modified NIH) diagnostic criteria for NF2 are shown in Table 1. […] Patients who have asymmetric involvement are likely to be mosaic. […] At very young ages ( 18 years) individuals presenting with an apparently isolated meningioma or vestibular schwannoma have a 20% and 10% likelihood respectively of developing NF2. […] The main differential diagnosis of NF2 is schwannomatosis and some patients with multiple non cranial schwannomas turn out to have mosaic NF2. […] Because detection of tumours at an early stage is effective in improving the clinical management of NF2, pre-symptomatic genetic testing is an integral part of the management of NF2 families.

• #35 Five recommendations for people with NF2 – Neurofibromatosis Midwest

  https://www.nfmidwest.org/blog/five-recommendations-people-nf2/

  Here is our advice: […] First NF2 is usually a slowly progressive disease, auditory tumors are ALWAYS benign and only grow about 1 mm per year on average and the symptoms (hearing loss, tinnitus, dizziness) are not always related to the the size of the tumors. […] Second We only perform surgical intervention when the benefit is greater than the risks. That is, we do not operate a tumor just because it is there and we do not prescribe chemotherapy or radiation therapy on NF2 tumors. […] Third The fact that your first symptoms appeared only after the age of 30 indicates that you probably have the least severe form of the disease, a slower progression, and fewer complications. The later the first symptom, the less severe the NF2. […] Fourth Your daughters chance of having inherited the NF2 from you is less than 50%, and may be as low as 25%, depending on some signs we find on the clinical examination. Heredity in NF2 is complex because in many cases, there is a mosaic form meaning only one part of your body has the mutation.

• #36 Investigations – NF2 – Oxford University Hospitals

  https://www.ouh.nhs.uk/nf2/investigations/

  MRI is used to: […] confirm the diagnosis of NF2. […] In NF2 we scan the brain and spine of all new patients. […] Genetic testing is used to find out whether a person is carrying a specific gene alteration that causes NF2. […] It is important to be aware that, even in people with a diagnosis of NF2, we do not always find a gene alteration to explain the diagnosis.

• #37 NF2-related schwannomatosis (NF2-SWN; formerly neurofibromatosis type 2) – UpToDate

  https://www.uptodate.com/contents/nf2-related-schwannomatosis-formerly-neurofibromatosis-type-2

  NF2-related schwannomatosis (NF2-SWN; formerly neurofibromatosis type 2) is an autosomal dominantly inherited syndrome that predisposes individuals to bilateral vestibular schwannomas as well as multiple other tumors of the nervous system. NF2-SWN is caused by pathogenic variants in the NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2) gene, which produces merlin, a tumor suppressor. […] The molecular pathogenesis, clinical features, diagnosis, and management of NF2-SWN are reviewed here. […] DIAGNOSIS Clinical and radiologic evaluation, Diagnostic criteria, Genetic testing, Differential diagnosis: Sporadic vestibular schwannomas, Other schwannomatoses, Neurofibromatosis type 1, Familial meningioma.

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

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

  Unless a person comes from a family with definite Schwannomatosis, the diagnosis is only considered after the more likely possibility of NF2 has been excluded. […] Patients with suspicious symptoms are usually referred to one of the specialist Neurofibromatosis (NF) Centres, or reviewed by Consultants working within a regional genetics service skilled at differentiating this diagnosis. […] The doctors there will undertake a series of tests to look for signs of NF2 including skin and eye checks, head and spine MRI scans and genetic testing. […] In an individual with at least 2 non-intradermal (i.e. within the layers of the skin) schwannomas, an MRI scan will be undertaken to confirm or exclude the diagnosis of NF2. […] If no vestibular schwannomas are present and there is no other evidence of NF2, then a diagnosis of Schwannomatosis will be considered. […] There is no confirmatory blood test available at present.

• #39 Neurofibromatosis type 2 | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/neurofibromatosis-type-2-3?lang=us

  Bilateral vestibular schwannomas are diagnostic of NF2 but care should be taken because bilateral internal acoustic meatus masses are not specific for vestibular schwannoma and can represent, for example, sarcoidosis or metastases. […] Although meningiomas are often isolated findings in adults, their presence in a child should raise suspicion of NF2. The presence of multiple and different types of spinal tumors also raise a high suspicion of NF2.

• #40 Diagnosis of sporadic neurofibromatosis type 2 in the paediatric population | Archives of Disease in Childhood

  https://adc.bmj.com/content/103/5/463

  Objective Onset of symptoms in severe sporadic neurofibromatosis type 2 (NF2) is typically within childhood; however, there is poor awareness of presenting features in young children, potentially resulting in delayed diagnosis and poorer outcome. […] We have reviewed presentation of sporadic paediatric NF2 to raise awareness of early features, highlighting those requiring further investigation. […] Epidemiological data estimate that 1 in 110611 births are affected with childhood-onset NF2. […] The mean delay to diagnosis was 3.16 years; in eight cases (25%) this exceeded 6 years. […] Most significant delay occurred in mononeuropathy, ophthalmological and/or seizure presentations, with a mean delay of 3, 4.5 and 6 years, respectively. […] All non-vestibular schwannoma NF2 presentations in childhood had significant diagnostic delay. […] We emphasise the importance of detailed assessment of skin and eyes in unusual presentations and propose an aide to prompt timely referral to specialist services.

• #41 Neurofibromatosis type 2 (NF2): A clinical and molecular review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-4-16

  Once a mutation has been identified in an affected individual, a 100% specific test is available for the family. […] In the absence of a genetic test a cumulative age at onset curve can be used. […] Even in the absence of identifying a mutation the residual risk of NF2 can be substantially reduced in the child of an apparently isolated case. […] Because of the severity of NF2 there is a demand for prenatal diagnosis and pre-implantation genetic diagnosis. […] Children of affected patients should be considered to be at 50% risk of NF2 and screening for NF2 can start at birth. […] Formal screening for VS should start at ten years, as it is rare for tumours to become symptomatic before that time even in severely affected families. […] In most families it is now possible to develop a genetic test so that screening can be targeted to affected individuals only.

• #42 Diagnostic and Prognostic Relevance of the Cutaneous Manifestations of Neurofibromatosis Type 2 | Actas Dermo-Sifiliográficas

  https://actasdermo.org/es-diagnostic-prognostic-relevance-cutaneous-manifestations-articulo-S1578219017302123

  Early diagnosis is even more important when NF2 presents in the early years of life. It has been shown that when the first symptoms of NF2 appear during childhood, the disease has a worse prognosis and mortality is higher. […] Dermatologists therefore have a crucial role for suspecting and confirming diagnosis of the disease, even though other tumors in the central or peripheral nervous systems are not present. […] In summary, NF2 is an uncommon disease that is associated with a high morbidity and mortality, above all when onset occurs during the first years of life. Early diagnosis of the process is a priority, as this improves survival and quality of life of the individuals affected.

• #43 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  MRI using 3-dimensional (3D) volumetrics is now the preferred method for following vestibular schwannoma growth over time. […] Hearing evaluations, including brainstem auditory-evoked response (BAER) may demonstrate latency abnormalities before a mass is detectable on MRI. […] Annual eye examinations are recommended for children and adults with NF2. […] Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression. […] Annual hearing screening with BAER, with referral to an audiologist for amplification, augmentation, or speech therapy recommendations. […] Annual MRI to monitor existing lesions or look for presymptomatic lesions. […] Annual ophthalmologic evaluations to monitor visual acuity.

• #44 NF2-Related Schwannomatosis – Children’s Tumor Foundation

  https://www.ctf.org/nf2-swn/

  Once someone has been diagnosed with NF2-SWN, several tests may help define the nature and progression of the disorder. These tests include the MRI (magnetic resonance imaging) scan and an audiometry, or hearing test. Oftentimes, an ophthalmological (eye) exam is recommended. Genetic testing can be done, which is a personal choice. It can be used to establish or confirm a diagnosis of NF2-SWN when the situation is uncertain. […] Healthcare providers use a list of diagnostic criteria (a checklist of signs and symptoms) to determine whether or not a patient may be given a diagnosis of a disorder or disease. A doctor will have to ask the patient many questions and thoroughly examine the individuals body to determine whether the criteria is met. Often, a patient will be asked to have genetic testing using a blood or saliva sample, or to have all or part of a tumor removed so that it can be viewed under a microscope.

• #45 79 Diagnosis and Evaluation of Neurofibromatosis Type 2 | Neupsy Key

  https://neupsykey.com/79-diagnosis-and-evaluation-of-neurofibromatosis-type-2/

  The clinical diagnostic criteria currently in use are shown in Table 791. […] While the presence of bilateral VS is a clear criterion for the diagnosis of NF2, some clinicians were concerned that the initial diagnostic criteria were overly restrictive, missing younger patients who would later develop full features of NF2. […] The finding of a VS or meningioma in a young person less than 30 years of age, for instance, raises suspicion for NF2 and although not all cases of VS in a young patient lead to later development of NF2, several patients will eventually develop NF2 based on clinical criteria. […] The behavior of VS in people with NF2 is highly variable with individual tumors following linear, sigmoid, logarithmic, and overall irregular growth curves based on traditional linear measurements on MRI. […] Given this variability, patients with NF2 are recommended to undergo MRI brain with thin cuts through the internal auditory canals at least annually and more frequently if there is evidence of active growth or if receiving treatment.

• #46 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  Its very important that your NF2 care is treated by a multidisciplinary team with experience caring for individuals with NF2. The treatment team includes: Neuro-oncologists. Neurosurgeons. ENT surgeons. Audiologists. Genetic counselors. […] A note from Cleveland Clinic NF2-related schwannomatosis (neurofibromatosis type 2) affects each person differently. Your symptoms can have a severe effect on how you go about your daily routine, or have little effect that only needs monitoring annually. Your care team will find treatment options to help you manage your symptoms. Theyll weigh each type of treatment to make sure its safe and that it offers the best outcome for you. If you plan on expanding your family and have a known biological history of neurofibromatosis, talk to your provider about genetic counseling.

• #47 Neurofibromatosis Type 2 Clinic – Overview – Mayo Clinic

  https://www.mayoclinic.org/departments-centers/neurofibromatosis-type-2-clinic/overview/ovc-20481871

  Neurofibromatosis type 2 (NF2) is an uncommon genetic condition that results in the development of multiple brain tumors and spinal tumors. […] At the Neurofibromatosis Type 2 Clinic at Mayo Clinic’s campus in Rochester, Minnesota, you will receive comprehensive care for the diagnosis and treatment of NF2. The clinic uses several new methods of genetic testing that detect nearly 100% of all mutations in the NF2 gene. […] During the week of your evaluation, you typically undergo an MRI study, hearing test and a neurological examination on Monday. […] The type of surgery depends on the size, type, location and depth of the tumor. […] Radiation therapy uses high-intensity beams of energy to treat tumors, including schwannomas and meningiomas. […] Chemotherapy uses drugs to stop tumor growth and, in some cases, to improve certain signs and symptoms of NF2, such as hearing loss. […] Depending on the size and location of the tumors, some people may need reconstructive surgery to restore facial nerve function and eye closure. […] At the Neurofibromatosis Type 2 Clinic, experts work together as a multispecialty team to provide exactly the care you need.

• #48 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  Its very important that your NF2 care is treated by a multidisciplinary team with experience caring for individuals with NF2. The treatment team includes: Neuro-oncologists. Neurosurgeons. ENT surgeons. Audiologists. Genetic counselors. […] A note from Cleveland Clinic NF2-related schwannomatosis (neurofibromatosis type 2) affects each person differently. Your symptoms can have a severe effect on how you go about your daily routine, or have little effect that only needs monitoring annually. Your care team will find treatment options to help you manage your symptoms. Theyll weigh each type of treatment to make sure its safe and that it offers the best outcome for you. If you plan on expanding your family and have a known biological history of neurofibromatosis, talk to your provider about genetic counseling.

• #49 Genetic Testing for Neurofibromatosis and Related Disorders AHS – M2134 | Providers | Blue Cross NC

  https://www.bluecrossnc.com/providers/policies-guidelines-codes/commercial/laboratory/updates/genetic-testing-for-neurofibromatosis-and-related-disorders

  Molecular testing approaches can differ for NF2 based on the clinical picture. Patients with the distinctive phenotypic and laboratory findings suggestive of NF2 are likely to be diagnosed using gene-targeted testing, whereas those where the diagnosis of NF2 has not been considered or had met the diagnostic criteria (such as children) are diagnosed after exome sequencing. […] Genetic testing for neurofibromatosis for all other situations not meeting the criteria outlined above is considered investigational.

• #50 Neurofibromatosis Type 2 Clinic – Overview – Mayo Clinic

  https://www.mayoclinic.org/departments-centers/neurofibromatosis-type-2-clinic/overview/ovc-20481871

  Neurofibromatosis type 2 (NF2) is an uncommon genetic condition that results in the development of multiple brain tumors and spinal tumors. […] At the Neurofibromatosis Type 2 Clinic at Mayo Clinic’s campus in Rochester, Minnesota, you will receive comprehensive care for the diagnosis and treatment of NF2. The clinic uses several new methods of genetic testing that detect nearly 100% of all mutations in the NF2 gene. […] During the week of your evaluation, you typically undergo an MRI study, hearing test and a neurological examination on Monday. […] The type of surgery depends on the size, type, location and depth of the tumor. […] Radiation therapy uses high-intensity beams of energy to treat tumors, including schwannomas and meningiomas. […] Chemotherapy uses drugs to stop tumor growth and, in some cases, to improve certain signs and symptoms of NF2, such as hearing loss. […] Depending on the size and location of the tumors, some people may need reconstructive surgery to restore facial nerve function and eye closure. […] At the Neurofibromatosis Type 2 Clinic, experts work together as a multispecialty team to provide exactly the care you need.

• #51 Neurofibromatosis Type 2 – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470350/

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors involving the central nervous system (CNS). […] The clinical diagnosis of NF2 is based on the presence of any 1 of the following criteria: […] Detailed clinical and family histories are required from the patients suspected of having NF2. A complete physical examination should be done to look for cutaneous schwannomas or plaque-like lesions, and an ophthalmic examination should be done to look for cataracts and optic nerve, among other things. […] For tumor surveillance, an annual brain MRI is recommended. If no brain tumor is seen on the initial imaging, then MRI can be done every 2 years. If the tumor is seen, an MRI should be done twice in the first year, followed by an annual follow-up. […] Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is a new systemic immunotherapy for many tumors. Some studies have shown tumor regression and hearing improvement in NF2 patients treated with bevacizumab.

• #52 Neurofibromatosis type 2 – diagnosis, features and MDT approach | Eye News

  https://www.eyenews.uk.com/education/top-tips/post/neurofibromatosis-type-2-diagnosis-features-and-mdt-approach

  NF2 is a genetic condition caused by mutation in a single gene (NF2 gene) on chromosome 22. […] The diagnosis of NF2 is confirmed by a thorough clinical evaluation and specialised testing (i.e., magnetic resonance imaging (MRI), audiometry, vision test, etc). […] A confirmed diagnosis of NF2 can be made if an individual has bilateral vestibular schwannomas (see table below). […] Early diagnosis and multidisciplinary management play a vital role in improving life expectancy and quality of life of affected individuals.

• #53 Diagnostic and Prognostic Relevance of the Cutaneous Manifestations of Neurofibromatosis Type 2 | Actas Dermo-Sifiliográficas

  https://actasdermo.org/es-diagnostic-prognostic-relevance-cutaneous-manifestations-articulo-S1578219017302123

  Skin lesions are not included in the criteria for diagnosis of the disease because it is generally thought that, unlike in neurofibromatosis type 1, skin manifestations in NF2 are uncommon and not very specific. However, nothing could be further from the truth; skin lesions in NF2, although not as frequent as in neurofibromatosis type 1, can be sufficiently characteristic to cause suspicion of the disease and even confirm diagnosis. […] The formation of cutaneous schwannomas is very characteristic of NF2 but not exclusive. […] Early diagnosis is essential to improve survival. This is useful for several reasons. First, it facilitates the detection of vestibular tumors while they are still small, thus enabling planning of the different therapeutic options available and it also gives the patients the chance to learn sign language while they are still able to hear (thus facilitating adaptation to the disease).

• #54 Diagnostic and Prognostic Relevance of the Cutaneous Manifestations of Neurofibromatosis Type 2 | Actas Dermo-Sifiliográficas

  https://actasdermo.org/es-diagnostic-prognostic-relevance-cutaneous-manifestations-articulo-S1578219017302123

  Early diagnosis is even more important when NF2 presents in the early years of life. It has been shown that when the first symptoms of NF2 appear during childhood, the disease has a worse prognosis and mortality is higher. […] Dermatologists therefore have a crucial role for suspecting and confirming diagnosis of the disease, even though other tumors in the central or peripheral nervous systems are not present. […] In summary, NF2 is an uncommon disease that is associated with a high morbidity and mortality, above all when onset occurs during the first years of life. Early diagnosis of the process is a priority, as this improves survival and quality of life of the individuals affected.

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