neurofibromatosis 2

Summary

Summary: An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.

Top Publications

  1. Ammoun S, Flaiz C, Ristic N, Schuldt J, Hanemann C. Dissecting and targeting the growth factor-dependent and growth factor-independent extracellular signal-regulated kinase pathway in human schwannoma. Cancer Res. 2008;68:5236-45 pubmed publisher
    ..We conclude that our schwannoma in vitro model can be used to screen for new therapeutic targets in general and that sorafenib is possible candidate for future clinical trials. ..
  2. Patel N, Mhatre A, Lalwani A. Molecular pathogenesis of skull base tumors. Otol Neurotol. 2004;25:636-43 pubmed
    ..Consistent progress is being made toward the molecular genetic and biological basis of the most common skull base tumors. An understanding of these mechanisms will aid the neurotologist in future diagnosis and management of the lesions. ..
  3. Hadfield K, Smith M, Urquhart J, Wallace A, Bowers N, King A, et al. Rates of loss of heterozygosity and mitotic recombination in NF2 schwannomas, sporadic vestibular schwannomas and schwannomatosis schwannomas. Oncogene. 2010;29:6216-21 pubmed publisher
    ..We found no evidence of MR in SMARCB1-positive schwannomatosis, suggesting that susceptibility to MR varies according to the disease context. ..
  4. Nunes F, MacCollin M. Neurofibromatosis 2 in the pediatric population. J Child Neurol. 2003;18:718-24 pubmed
    b>Neurofibromatosis 2 is a severe autosomal dominant disorder characterized by the occurrence of bilateral vestibular schwannomas and other benign tumors of the nervous system...
  5. Golovnina K, Blinov A, Akhmametyeva E, Omelyanchuk L, Chang L. Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene. BMC Evol Biol. 2005;5:69 pubmed
    ..The overall similarity among the primary and secondary structures of all merlin proteins and the conservation of several functionally important residues suggest a universal role for merlin in a wide range of metazoa. ..
  6. Casar Borota O, Jacobsen E, Scheie D. Bilateral atypical choroid plexus papillomas in cerebellopontine angles mimicking neurofibromatosis 2. Acta Neuropathol. 2006;111:500-2 pubmed
  7. Phi J, Kim D, Chung H, Lee J, Paek S, Jung H. Radiosurgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2: tumor control and hearing preservation. Cancer. 2009;115:390-8 pubmed publisher
    ..The rates of other cranial nerve deficits were low, and no secondary malignancy was observed. Radiosurgery should be included in treatment options for NF2 patients. ..
  8. Tsilchorozidou T, Menko F, Lalloo F, Kidd A, De Silva R, Thomas H, et al. Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2. J Med Genet. 2004;41:529-34 pubmed
  9. Fisher L, Doherty J, Lev M, Slattery W. Distribution of nonvestibular cranial nerve schwannomas in neurofibromatosis 2. Otol Neurotol. 2007;28:1083-90 pubmed
    ..and location of cranial nerve schwannomas, other than bilateral vestibular schwannoma, in patients with neurofibromatosis 2 (NF2)...

More Information

Publications71

  1. Baser M, Friedman J, Evans D. Increasing the specificity of diagnostic criteria for schwannomatosis. Neurology. 2006;66:730-2 pubmed
    ..In this study, the authors use data from the population-based United Kingdom NF2 Registry to recommend modifications that increase the specificity of the schwannomatosis diagnostic criteria...
  2. Pascual Castroviejo I, Pascual Pascual S, Viano J. [Neurofibromatosis type 2 (NF2). Study of 7 patients]. Neurologia. 2009;24:457-61 pubmed
    ..The aim of this paper is to present the cases of 7 young children and young adult with type 2 neurofibromatosis (NF2)...
  3. Hanemann C, Bartelt Kirbach B, Diebold R, Kämpchen K, Langmesser S, Utermark T. Differential gene expression between human schwannoma and control Schwann cells. Neuropathol Appl Neurobiol. 2006;32:605-14 pubmed
    ..Regulated clones, some of which not been described in Schwann cells earlier, included matrix metalloproteinase's, growth factors, growth factor receptors and tyrosine kinases...
  4. Angelo L, Wu J, Meng F, Sun M, Kopetz S, McCutcheon I, et al. Combining curcumin (diferuloylmethane) and heat shock protein inhibition for neurofibromatosis 2 treatment: analysis of response and resistance pathways. Mol Cancer Ther. 2011;10:2094-103 pubmed publisher
    ..The combination of curcumin and an hsp inhibitor synergistically suppressed schwannoma cell growth. Our results provide a rationale for combining curcumin and KNK437 in the treatment of NF2...
  5. Evans D, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol. 2005;26:93-7 pubmed
    ..To determine the incidence of vestibular schwannoma (VS) in sporadic, neurofibromatosis type 2 (NF2) germ-line and mosaic form in a 10-year period...
  6. Rong R, Surace E, Haipek C, Gutmann D, Ye K. Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression. Oncogene. 2004;23:8447-54 pubmed
    The neurofibromatosis 2 (NF2) tumor suppressor protein, merlin, functions as a negative growth regulator; however, the molecular mechanisms that underlie merlin regulation remain elusive...
  7. Plotkin S, Singh M, O Donnell C, Harris G, McClatchey A, Halpin C. Audiologic and radiographic response of NF2-related vestibular schwannoma to erlotinib therapy. Nat Clin Pract Oncol. 2008;5:487-91 pubmed publisher
    ..A 48-year-old man presented to a neurologist with complaints of bilateral hearing loss and tinnitus. The patient was a member of a large family affected by neurofibromatosis type 2 and first noted hearing loss 10 years before presentation...
  8. Evans D, Howard E, Giblin C, Clancy T, Spencer H, Huson S, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A:327-32 pubmed publisher
    ..Estimates for NF1, NF2, FAP, and VHL are in line with previous estimates, and we provide the first estimates of birth incidence and de novo mutation rate for GS...
  9. Rowe J, Radatz M, Walton L, Soanes T, Rodgers J, Kemeny A. Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis. J Neurol Neurosurg Psychiatry. 2003;74:1288-93 pubmed
    ..To evaluate the results of stereotactic radiosurgery treating vestibular schwannomas secondary to type 2 neurofibromatosis...
  10. Rong R, Tang X, Gutmann D, Ye K. Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L. Proc Natl Acad Sci U S A. 2004;101:18200-5 pubmed
    b>Neurofibromatosis 2 (NF2) is a tumor suppressor, although the molecular mechanism accounting for this effect remains unknown...
  11. Stemmer Rachamimov A, Louis D, Nielsen G, Antonescu C, Borowsky A, Bronson R, et al. Comparative pathology of nerve sheath tumors in mouse models and humans. Cancer Res. 2004;64:3718-24 pubmed
    ..A novel classification scheme for peripheral nerve sheath tumors in murine models was therefore devised...
  12. Scoles D. The merlin interacting proteins reveal multiple targets for NF2 therapy. Biochim Biophys Acta. 2008;1785:32-54 pubmed
    The neurofibromatosis 2 (NF2) tumor suppressor protein merlin is commonly mutated in human benign brain tumors. The gene altered in NF2 was located on human chromosome 22q12 in 1993 and the encoded protein named merlin and schwannomin...
  13. Thaxton C, Bott M, Walker B, Sparrow N, Lambert S, Fernandez Valle C. Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length. Mol Cell Neurosci. 2011;47:1-9 pubmed publisher
    ..By stabilizing the bipolar morphology, Sch promotes the alignment of SCs with axons and ultimately influences myelin segment length...
  14. Gonzalez Gomez P, Bello M, Alonso M, Lomas J, Arjona D, Campos J, et al. CpG island methylation in sporadic and neurofibromatis type 2-associated schwannomas. Clin Cancer Res. 2003;9:5601-6 pubmed
    ..The purpose of this research was to examine the DNA methylation profile of schwannomas...
  15. Lenarz T, Lim H, Reuter G, Patrick J, Lenarz M. The auditory midbrain implant: a new auditory prosthesis for neural deafness-concept and device description. Otol Neurotol. 2006;27:838-43 pubmed
    ..Practical considerations for implementation of the AMI will also be discussed...
  16. Baser M. The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene. Hum Mutat. 2006;27:297-306 pubmed
    Constitutional heterozygous inactivating mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene cause the autosomal dominant disease NF2, and biallelic inactivating somatic NF2 mutations are found in a high proportion of ..
  17. Yohay K. Neurofibromatosis types 1 and 2. Neurologist. 2006;12:86-93 pubmed
    ..Both disorders have widely variable presentations and degrees of severity. A thorough understanding of these complex disorders is essential for proper medical management, anticipatory care, and patient education...
  18. Berg J, Scheithauer B, Spinner R, Allen C, Koutlas I. Plexiform schwannoma: a clinicopathologic overview with emphasis on the head and neck region. Hum Pathol. 2008;39:633-40 pubmed publisher
    ..Furthermore, the association with neurofibromatosis type 2 and with schwannomatosis was 5% each...
  19. Flaiz C, Utermark T, Parkinson D, Poetsch A, Hanemann C. Impaired intercellular adhesion and immature adherens junctions in merlin-deficient human primary schwannoma cells. Glia. 2008;56:506-15 pubmed publisher
  20. McClatchey A. Neurofibromatosis. Annu Rev Pathol. 2007;2:191-216 pubmed
    ..An important outcome of the study of neurofibromatosis-associated tumorigenesis has been insight into the more general molecular and cellular bases of nervous system tumors...
  21. Plotkin S, Stemmer Rachamimov A, Barker F, Halpin C, Padera T, Tyrrell A, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361:358-67 pubmed publisher
    ..There is no medical treatment for such tumors...
  22. Aghi M, Kluwe L, Webster M, Jacoby L, Barker F, Ojemann R, et al. Unilateral vestibular schwannoma with other neurofibromatosis type 2-related tumors: clinical and molecular study of a unique phenotype. J Neurosurg. 2006;104:201-7 pubmed
    ..The authors studied the clinical course and genetic basis of unilateral VSs associated with other NF2-related tumors...
  23. Utermark T, Kaempchen K, Hanemann C. Pathological adhesion of primary human schwannoma cells is dependent on altered expression of integrins. Brain Pathol. 2003;13:352-63 pubmed
  24. Kissil J, Wilker E, Johnson K, Eckman M, Yaffe M, Jacks T. Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell. 2003;12:841-9 pubmed
    ..This link provides a possible mechanism for the effect of loss of merlin expression in tumorigenesis...
  25. Evans D, Baser M, O Reilly B, Rowe J, Gleeson M, Saeed S, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg. 2005;19:5-12 pubmed
    A consensus conference on neurofibromatosis 2 (NF2) was held in 2002 at the request of the United Kingdom (UK) Neurofibromatosis Association, with particular emphasis on vestibular schwannoma (VS) surgery...
  26. Plotkin S, Merker V, Halpin C, Jennings D, McKenna M, Harris G, et al. Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012;33:1046-52 pubmed publisher
    ..The aim of this study was to report extended follow-up in a larger cohort of similarly treated patients...
  27. McCreery D. Cochlear nucleus auditory prostheses. Hear Res. 2008;242:64-73 pubmed publisher
    ..This suggests that the cochlear nuclei of the NF2 patients are damaged by the disease process or during surgical removal of the tumor...
  28. Selvanathan S, Shenton A, Ferner R, Wallace A, Huson S, Ramsden R, et al. Further genotype--phenotype correlations in neurofibromatosis 2. Clin Genet. 2010;77:163-70 pubmed publisher
    b>Neurofibromatosis 2 (NF2) is caused by mutations in the NF2 gene predisposing carriers to develop nervous system tumours...
  29. Ammoun S, Schmid M, Ristic N, Zhou L, Hilton D, Ercolano E, et al. The role of insulin-like growth factors signaling in merlin-deficient human schwannomas. Glia. 2012;60:1721-33 pubmed publisher
    ..PI3K is relevant for both IGF-IR and previously described PDGFR-? signaling in schwannoma...
  30. Masuda A, Fisher L, Oppenheimer M, Iqbal Z, Slattery W. Hearing changes after diagnosis in neurofibromatosis type 2. Otol Neurotol. 2004;25:150-4 pubmed
    ..Describe the changes in hearing ability and progression of disease over time in subjects with neurofibromatosis Type 2 enrolled in a multicenter natural history study of vestibular schwannomas in neurofibromatosis Type 2...
  31. Baser M, Kuramoto L, Joe H, Friedman J, Wallace A, Gillespie J, et al. Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population-based study. Am J Hum Genet. 2004;75:231-9 pubmed
    b>Neurofibromatosis 2 (NF2) is an autosomal dominant disease that is characterized by tumors on the vestibular branch of the VIII cranial nerve, but other types of nervous system tumors usually occur as well...
  32. Schwartz M, Otto S, Shannon R, Hitselberger W, Brackmann D. Auditory brainstem implants. Neurotherapeutics. 2008;5:128-36 pubmed publisher
    ..We discuss future directions in central implants for hearing, including the penetrating ABI, the use of ABI in nontumor patients, and the auditory midbrain implant...
  33. Dow G, Biggs N, Evans G, Gillespie J, Ramsden R, King A. Spinal tumors in neurofibromatosis type 2. Is emerging knowledge of genotype predictive of natural history?. J Neurosurg Spine. 2005;2:574-9 pubmed
  34. Baumer P, Mautner V, Baumer T, Schuhmann M, Tatagiba M, Heiland S, et al. Accumulation of non-compressive fascicular lesions underlies NF2 polyneuropathy. J Neurol. 2013;260:38-46 pubmed publisher
    ..Additionally, the results underscore the feasibility of this new method, which may open up new diagnostic and investigative possibilities for other disseminated disorders of the peripheral nervous system...
  35. Baser M, Rai H, Wallace A, Evans D. Neurofibromatosis 2 (NF2) and malignant mesothelioma in a man with a constitutional NF2 missense mutation. Fam Cancer. 2005;4:321-2 pubmed
    b>Neurofibromatosis 2 (NF2) is caused by inactivating mutations of the NF2 tumor suppressor gene. Somatic NF2 mutations also occur in a high proportion of human primary malignant mesotheliomas...
  36. Slattery W, Hoa M, Bonne N, Friedman R, Schwartz M, Fisher L, et al. Middle fossa decompression for hearing preservation: a review of institutional results and indications. Otol Neurotol. 2011;32:1017-24 pubmed publisher
    ..To assess the duration of hearing preservation from time of vestibular schwannoma middle fossa decompression with short-term and 1-year hearing preservation rates...
  37. Ruggieri M, Iannetti P, Polizzi A, La Mantia I, Spalice A, Giliberto O, et al. Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: a study of 24 patients. Neuropediatrics. 2005;36:21-34 pubmed
    ..Although classically considered a disease of adults, initial signs and/or symptoms may be evident in childhood and are often unrecognised...
  38. Surace E, Haipek C, Gutmann D. Effect of merlin phosphorylation on neurofibromatosis 2 (NF2) gene function. Oncogene. 2004;23:580-7 pubmed
    The neurofibromatosis 2 (NF2) tumor suppressor gene product, merlin, belongs to the ezrin-radixin-moesin (ERM) subgroup of the Protein 4.1 family, which links cell surface glycoproteins to the actin cytoskeleton...
  39. Ferner R. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol. 2007;6:340-51 pubmed
    Historically, neurofibromatosis 1 (NF1) has been inextricably linked with neurofibromatosis 2 (NF2)...
  40. Evans D, Ramsden R, Shenton A, Gokhale C, Bowers N, Huson S, et al. Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification. J Med Genet. 2007;44:424-8 pubmed
    ..Neurofibromatosis type 2 (NF2) is almost unique among inherited disorders in the frequency of mosaicism in the first affected generation. However, the implications of this on transmission risks have not been fully elucidated...
  41. Xiao G, Chernoff J, Testa J. NF2: the wizardry of merlin. Genes Chromosomes Cancer. 2003;38:389-99 pubmed
    ..In this review, we summarize the involvement of NF2 inactivation in tumorigenesis. We also discuss observations implicating merlin in cell motility and cell proliferation, with a focus on recent findings linking merlin to Rac signaling...
  42. Plotkin S, Halpin C, McKenna M, Loeffler J, Batchelor T, Barker F. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol. 2010;31:1135-43 pubmed publisher
    ..We sought to determine the activity of erlotinib for progressive vestibular schwannoma (VS) associated with neurofibromatosis 2 (NF2).
  43. Schulz A, Baader S, Niwa Kawakita M, Jung M, Bauer R, Garcia C, et al. Merlin isoform 2 in neurofibromatosis type 2-associated polyneuropathy. Nat Neurosci. 2013;16:426-33 pubmed publisher
    ..Sciatic nerves from these mice and sural nerve biopsies from NF2 patients revealed reduced phosphorylation of the neurofilament H subunit, decreased interfilament spacings and irregularly shaped axons...
  44. Otsuka G, Saito K, Nagatani T, Yoshida J. Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2. J Neurosurg. 2003;99:480-3 pubmed
    ..To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2...
  45. Warren C, James L, Ramsden R, Wallace A, Baser M, Varley J, et al. Identification of recurrent regions of chromosome loss and gain in vestibular schwannomas using comparative genomic hybridisation. J Med Genet. 2003;40:802-6 pubmed
    ..The GTPase signalling molecules RhoA and Rac1 regulate merlin function, but to date only mutation in the NF2 gene has been identified as a causal event in schwannoma formation...
  46. MacCollin M, Chiocca E, Evans D, Friedman J, Horvitz R, Jaramillo D, et al. Diagnostic criteria for schwannomatosis. Neurology. 2005;64:1838-45 pubmed
    ..Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself...
  47. Yamauchi J, Miyamoto Y, Kusakawa S, Torii T, Mizutani R, Sanbe A, et al. Neurofibromatosis 2 tumor suppressor, the gene induced by valproic acid, mediates neurite outgrowth through interaction with paxillin. Exp Cell Res. 2008;314:2279-88 pubmed publisher
    ..These results suggest that merlin is an as yet unknown regulator of neurite outgrowth through the interaction with paxillin, providing a possibly common mechanism regulating neurite formation...
  48. Asthagiri A, Parry D, Butman J, Kim H, Tsilou E, Zhuang Z, et al. Neurofibromatosis type 2. Lancet. 2009;373:1974-86 pubmed publisher
    ..We review the molecular pathogenesis, genetics, clinical findings, and management strategies for neurofibromatosis type 2. ..
  49. Hoa M, Slattery W. Neurofibromatosis 2. Otolaryngol Clin North Am. 2012;45:315-32, viii pubmed publisher
    A comprehensive discussion of neurofibromatosis 2 (NF2) is presented, including clinical characteristics, symptoms, diagnosis, tumor types, prevalence and incidence, genetic testing, imaging, treatment options, and follow-up management ..
  50. Davidson T, Sanchez Lara P, Randolph L, Krieger M, Wu S, Panigrahy A, et al. Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature. BMC Med Genet. 2012;13:19 pubmed publisher
    ..2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient...
  51. Hanemann C. Magic but treatable? Tumours due to loss of merlin. Brain. 2008;131:606-15 pubmed
    ..Finally, I will discuss how loss of merlin leads to tumourigenesis in order to understand the rationale for emerging new therapeutic targets...
  52. Evans D. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis. 2009;4:16 pubmed publisher
    ..In the future, the development of tailored drug therapies aimed at the genetic level are likely to provide huge improvements for this devastating condition...
  53. Smith M, Higgs J, Bowers N, Halliday D, Paterson J, Gillespie J, et al. Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset. J Med Genet. 2011;48:261-5 pubmed publisher
    ..The spectrum of NF2 mutations consists mainly of truncating (nonsense and frameshift) mutations. A smaller number of patients have missense mutations, which are associated with a milder disease phenotype...
  54. Yang C, Asthagiri A, Iyer R, Lu J, Xu D, Ksendzovsky A, et al. Missense mutations in the NF2 gene result in the quantitative loss of merlin protein and minimally affect protein intrinsic function. Proc Natl Acad Sci U S A. 2011;108:4980-5 pubmed publisher
    ..These findings provide direct insight into protein function and tumorigenesis in NF2 and indicate a unique treatment paradigm for this disorder...
  55. Yi C, Wilker E, Yaffe M, Stemmer Rachamimov A, Kissil J. Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2. Cancer Res. 2008;68:7932-7 pubmed publisher
    ..In addition, the finding that the shRNA-mediated Pak1 suppression was silenced rapidly by methylation raises questions about the future application of such technologies for the treatment of diseases such as cancer...
  56. Chang Z, Guo C, Ahronowitz I, Stemmer Rachamimov A, MacCollin M, Nunes F. A role for the p53 pathway in the pathology of meningiomas with NF2 loss. J Neurooncol. 2009;91:265-70 pubmed publisher
    The neurofibromatosis 2 locus (NF2) is inactivated through mutation and loss of heterozygosity (LOH) in 40-65% of all sporadic meningiomas, while the role of the p53 tumor suppression pathway in meningioma initiation and progression is ..
  57. Fisher L, Doherty J, Lev M, Slattery W. Concordance of bilateral vestibular schwannoma growth and hearing changes in neurofibromatosis 2: neurofibromatosis 2 natural history consortium. Otol Neurotol. 2009;30:835-41 pubmed publisher
    To examine the relationship between the amount of change in size and associated hearing in bilateral vestibular schwannomas (VSs) in persons with neurofibromatosis 2 (NF2).
  58. Evans D, Ramsden R, Gokhale C, Bowers N, Huson S, Wallace A. Should NF2 mutation screening be undertaken in patients with an apparently isolated vestibular schwannoma?. Clin Genet. 2007;71:354-8 pubmed
    ..Germ line mutation testing is probably only justified in sporadic unilateral VS <20 years unless other features of NF2 are present. Ideally mutation testing should start with the original tumour specimen...
  59. Bosch M, Boltshauser E, Harpes P, Landau K. Ophthalmologic findings and long-term course in patients with neurofibromatosis type 2. Am J Ophthalmol. 2006;141:1068-1077 pubmed
    ..To evaluate ophthalmologic findings and long-term course in patients with neurofibromatosis type 2 (NF2)...
  60. Slattery W, Lev M, Fisher L, Connell S, Iqbal Z, Go J. MRI evaluation of neurofibromatosis 2 patients: a standardized approach for accuracy in interpretation. Otol Neurotol. 2005;26:733-40 pubmed
    ..To determine the level of agreement between local radiologists' and an experienced neuroradiologist's measurements of vestibular schwannomas...
  61. Baser M, Kuramoto L, Woods R, Joe H, Friedman J, Wallace A, et al. The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2. J Med Genet. 2005;42:540-6 pubmed
    b>Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown...
  62. Cai W, Kassarjian A, Bredella M, Harris G, Yoshida H, Mautner V, et al. Tumor burden in patients with neurofibromatosis types 1 and 2 and schwannomatosis: determination on whole-body MR images. Radiology. 2009;250:665-73 pubmed publisher