Neurofi bromatosis type 2 Syndrome
Abstract
Neurofi bromatosis type 2 (NF2) is a dominantly inherited syndrome that causes several tumors of the nervous system in affected individuals. Mutations in the NF2 gene cause neurofi bromatosis type 2. The NF2 gene provides instructions for producing a protein called merlin, a cell membrane-related protein that acts as a tumor suppressor. Recent studies estimate that the incidence of neurofi bromatosis type 2 may be as high as 1 in 25,000 people. The symptoms of neurofi bromatosis type 2 are typically noticed between 18 to 22 years of age. The most common fi rst symptom is hearing loss or tinnitus. The clinical presentations of NF2 include bilateral vestibular schwannomas. Other commonly observed nervous system tumors include intracranial meningiomas, schwannomas of other cranial nerves, and spinal tumors. Neuropathies and ocular and cutaneous manifestations are also frequent. The clinical diagnosis of NF2 is based upon the National Institutes of Health consensus criteria as subsequently modifi ed in the Manchester criteria. The differential diagnosis includes sporadic unilateral vestibular schwannomas, neurofi bromatosis type 1, schwannomatosis, and familial meningiomas. Although the treatment of the various clinical manifestations of NF2 is similar to that for sporadic tumors of the same particular type, multidisciplinary team approach is required to minimize the potential morbidities caused by treatment.
References
Evans DG. Neurofi bromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis 2009; 4:16.
Evans DG. Neurofi bromatosis 2 [Bilateral acoustic neurofi bromatosis, central neurofi bromatosis, NF2, neurofi bromatosis type II]. Genet Med 2009; 11:599.
Asthagiri AR, Parry DM, Butman JA, et al. Neurofi bromatosis type 2. Lancet 2009; 373:1974.
Seizinger BR, Martuza RL, Gusella JF. Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature 1986; 322:644.
Rouleau GA, Merel P, Lutchman M, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fi bromatosis type 2. Nature 1993; 363:515.
Trofatter JA, MacCollin MM, Rutter JL, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofi bromatosis 2 tumor suppressor. Cell 1993; 72:791.
Evans DG, Ramsden RT, Shenton A, et al. Mosaicism in neurofi bromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplifi cation. J Med Genet 2007; 44:424.
Kluwe L, Mautner V, Heinrich B, et al. Molecular study of frequency of mosaicism in neurofi bromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 2003; 40:109.
Moyhuddin A, Baser ME, Watson C, et al. Somatic mosaicism in neurofi bromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet 2003; 40:459.
Evans DG, Wallace AJ, Wu CL, et al. Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis. Am J Hum Genet 1998; 63:727.
Selvanathan SK, Shenton A, Ferner R, et al. Further genotype--phenotype correlations in neurofi bromatosis 2. Clin Genet 2010; 77:163.
Evans DG, Moran A, King A, et al. Incidence of vestibular schwannoma and neurofi bromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol 2005; 26:93.
Evans DG, Howard E, Giblin C, 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.
Antinheimo J, Sankila R, Carpen O, et al. Population-based analysis of sporadic and type 2 neurofi bromatosis-associated meningiomas and schwannomas. Neurology 2000; 54:71.
Parry DM, Eldridge R, Kaiser-Kupfer MI, et al. Neurofi bromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet 1994; 52:450.
Mautner VF, Lindenau M, Baser ME, et al. The neuroimaging and clinical spectrum of neurofi bromatosis 2. Neurosurgery 1996; 38:880.
Evans DG, Huson SM, Donnai D, et al. A clinical study of type 2 neurofi bromatosis. Q J Med 1992; 84:603.
Bosch MM, Boltshauser E, Harpes P, Landau K. Ophthalmologic fi ndings and long-term course in patients with neurofi bromatosis type 2. Am J Ophthalmol 2006; 141:1068.
Ragge NK, Baser ME, Riccardi VM, Falk RE. The ocular presentation of neurofi bromatosis 2. Eye (Lond) 1997; 11 ( Pt 1):12.
Ragge NK, Baser ME, Klein J, et al. Ocular abnormalities in neurofi bromatosis 2. Am J Ophthalmol 1995; 120:634.
MacCollin M, Mautner VF. The diagnosis and management of neurofi bromatosis 2 in childhood. Semin Pediatr Neurol 1998; 5:243.
Mautner VF, Lindenau M, Baser ME, et al. Skin abnormalities in neurofi bromatosis 2. Arch Dermatol 1997; 133:1539.
Evans DG, Birch JM, Ramsden RT. Paediatric presentation of type 2 neurofi bromatosis. Arch Dis Child 1999; 81:496.
Evans DG, Watson C, King A, et al. Multiple meningiomas: differential involvement of the NF2 gene in children and adults. J Med Genet 2005; 42:45.
Perry A, Giannini C, Raghavan R, et al. Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: a clinicopathologic study of 53 cases. J Neuropathol Exp Neurol 2001; 60:994.
Larson JJ, van Loveren HR, Balko MG, Tew JM Jr. Evidence of meningioma infi ltration into cranial nerves: clinical implications for cavernous sinus meningiomas. J Neurosurg 1995; 83:596.
Patronas NJ, Courcoutsakis N, Bromley CM, et al. Intramedullary and spinal canal tumors in patients with neurofi bromatosis 2: MR imaging fi ndings and correlation with genotype. Radiology 2001; 218:434.
Dow G, Biggs N, Evans G, et al. Spinal tumors in neurofi bromatosis type 2. Is emerging knowledge of genotype predictive of natural history?. J Neurosurg Spine 2005; 2:574.
Sperfeld AD, Hein C, Schroder JM, et al. Occurrence and characterization of peripheral nerve involvement in neurofi bromatosis type 2. Brain 2002; 125:996.
McLaughlin ME, Pepin SM, Maccollin M, et al. Ocular pathologic fi ndings of neurofi bromatosis type 2. Arch Ophthalmol 2007; 125:389.
Neurofi bromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol 1988; 45:575.
Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofi bromatosis 1 and neurofi bromatosis 2. JAMA 1997; 278:51.
Evans DG, Baser ME, O'Reilly B, et al. Management of the patient and family with neurofi bromatosis 2: a consensus conference statement. Br J Neurosurg 2005; 19:5.
Evans DG, Ramsden RT, Gokhale C, et al. Should NF2 mutation screening be undertaken in patients with an apparently isolated vestibular schwannoma?. Clin Genet 2007; 71:354.
Mohyuddin A, Neary WJ, Wallace A, et al. Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas. J Med Genet 2002; 39:315.
Kida Y, Kobayashi T, Tanaka T, Mori Y. Radiosurgery for bilateral neurinomas associated with neurofi bromatosis type 2. Surg Neurol 2000; 53:383.
Mathieu D, Kondziolka D, Flickinger JC, et al. Stereotactic radiosurgery for vestibular schwannomas in patients with neurofi bromatosis type 2: an analysis of tumor control, complications, and hearing preservation rates. Neurosurgery 2007; 60:460.
Roche PH, Regis J, Pellet W, et al. [Neurofi bromatosis type 2. Preliminary results of gamma knife radiosurgery of vestibular schwannomas]. Neurochirurgie 2000; 46:339.
Rowe JG, Radatz MW, Walton L, et al. Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofi bromatosis. J Neurol Neurosurg Psychiatry 2003; 74:1288.
Baser ME, Evans DG, Jackler RK, et al. Neurofi bromatosis 2, radiosurgery and malignant nervous system tumours. Br J Cancer 2000; 82:998.
Evans DG, Birch JM, Ramsden RT, et al. Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 2006; 43:289.
Balasubramaniam A, Shannon P, Hodaie M, et al. Glioblastoma multiforme after stereotactic radiotherapy for acoustic neuroma: Case report and review of the literature. Neuro Oncol 2007; 9:447.
Neff BA, Wiet RM, Lasak JM, et al. Cochlear implantation in the neurofi bromatosis type 2 patient: long-term follow-up. Laryngoscope 2007; 117:1069.
Wentworth S, Pinn M, Bourland JD, et al. Clinical experience with radiation therapy in the management of neurofi bromatosis-associated central nervous system tumors. Int J Radiat Oncol Biol Phys 2009; 73:208.
Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofi bromatosis type 2. Neuro Oncol 2010; 12:14.
Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofi bromatosis type 2. N Engl J Med 2009; 361:358.
Ruggieri M, Iannetti P, Polizzi A, et al. Earliest clinical manifestations and natural history of neurofi bromatosis type 2 (NF2) in childhood: a study of 24 patients. Neuropediatrics 2005; 36:21.
Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofi bromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol 1993; 52:106.
Evans DG, Huson SM, Donnai D, et al. A genetic study of type 2 neurofi bromatosis in the United Kingdom. I. Prevalence, mutation rate, fi tness, and confi rmation of maternal transmission effect on severity. J Med Genet 1992; 29:841.
Evans DG, Huson SM, Donnai D, et al. A genetic study of type 2 neurofi bromatosis in the United Kingdom. II. Guidelines for genetic counselling. J Med Genet 1992; 29:847.
Baser ME, Friedman JM, Aeschliman D, et al. Predictors of the risk of mortality in neurofi bromatosis 2. Am J Hum Genet 2002; 71:715.
Evans DG. Neurofi bromatosis 2 [Bilateral acoustic neurofi bromatosis, central neurofi bromatosis, NF2, neurofi bromatosis type II]. Genet Med 2009; 11:599.
Asthagiri AR, Parry DM, Butman JA, et al. Neurofi bromatosis type 2. Lancet 2009; 373:1974.
Seizinger BR, Martuza RL, Gusella JF. Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature 1986; 322:644.
Rouleau GA, Merel P, Lutchman M, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fi bromatosis type 2. Nature 1993; 363:515.
Trofatter JA, MacCollin MM, Rutter JL, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofi bromatosis 2 tumor suppressor. Cell 1993; 72:791.
Evans DG, Ramsden RT, Shenton A, et al. Mosaicism in neurofi bromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplifi cation. J Med Genet 2007; 44:424.
Kluwe L, Mautner V, Heinrich B, et al. Molecular study of frequency of mosaicism in neurofi bromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 2003; 40:109.
Moyhuddin A, Baser ME, Watson C, et al. Somatic mosaicism in neurofi bromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet 2003; 40:459.
Evans DG, Wallace AJ, Wu CL, et al. Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis. Am J Hum Genet 1998; 63:727.
Selvanathan SK, Shenton A, Ferner R, et al. Further genotype--phenotype correlations in neurofi bromatosis 2. Clin Genet 2010; 77:163.
Evans DG, Moran A, King A, et al. Incidence of vestibular schwannoma and neurofi bromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol 2005; 26:93.
Evans DG, Howard E, Giblin C, 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.
Antinheimo J, Sankila R, Carpen O, et al. Population-based analysis of sporadic and type 2 neurofi bromatosis-associated meningiomas and schwannomas. Neurology 2000; 54:71.
Parry DM, Eldridge R, Kaiser-Kupfer MI, et al. Neurofi bromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet 1994; 52:450.
Mautner VF, Lindenau M, Baser ME, et al. The neuroimaging and clinical spectrum of neurofi bromatosis 2. Neurosurgery 1996; 38:880.
Evans DG, Huson SM, Donnai D, et al. A clinical study of type 2 neurofi bromatosis. Q J Med 1992; 84:603.
Bosch MM, Boltshauser E, Harpes P, Landau K. Ophthalmologic fi ndings and long-term course in patients with neurofi bromatosis type 2. Am J Ophthalmol 2006; 141:1068.
Ragge NK, Baser ME, Riccardi VM, Falk RE. The ocular presentation of neurofi bromatosis 2. Eye (Lond) 1997; 11 ( Pt 1):12.
Ragge NK, Baser ME, Klein J, et al. Ocular abnormalities in neurofi bromatosis 2. Am J Ophthalmol 1995; 120:634.
MacCollin M, Mautner VF. The diagnosis and management of neurofi bromatosis 2 in childhood. Semin Pediatr Neurol 1998; 5:243.
Mautner VF, Lindenau M, Baser ME, et al. Skin abnormalities in neurofi bromatosis 2. Arch Dermatol 1997; 133:1539.
Evans DG, Birch JM, Ramsden RT. Paediatric presentation of type 2 neurofi bromatosis. Arch Dis Child 1999; 81:496.
Evans DG, Watson C, King A, et al. Multiple meningiomas: differential involvement of the NF2 gene in children and adults. J Med Genet 2005; 42:45.
Perry A, Giannini C, Raghavan R, et al. Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: a clinicopathologic study of 53 cases. J Neuropathol Exp Neurol 2001; 60:994.
Larson JJ, van Loveren HR, Balko MG, Tew JM Jr. Evidence of meningioma infi ltration into cranial nerves: clinical implications for cavernous sinus meningiomas. J Neurosurg 1995; 83:596.
Patronas NJ, Courcoutsakis N, Bromley CM, et al. Intramedullary and spinal canal tumors in patients with neurofi bromatosis 2: MR imaging fi ndings and correlation with genotype. Radiology 2001; 218:434.
Dow G, Biggs N, Evans G, et al. Spinal tumors in neurofi bromatosis type 2. Is emerging knowledge of genotype predictive of natural history?. J Neurosurg Spine 2005; 2:574.
Sperfeld AD, Hein C, Schroder JM, et al. Occurrence and characterization of peripheral nerve involvement in neurofi bromatosis type 2. Brain 2002; 125:996.
McLaughlin ME, Pepin SM, Maccollin M, et al. Ocular pathologic fi ndings of neurofi bromatosis type 2. Arch Ophthalmol 2007; 125:389.
Neurofi bromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol 1988; 45:575.
Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofi bromatosis 1 and neurofi bromatosis 2. JAMA 1997; 278:51.
Evans DG, Baser ME, O'Reilly B, et al. Management of the patient and family with neurofi bromatosis 2: a consensus conference statement. Br J Neurosurg 2005; 19:5.
Evans DG, Ramsden RT, Gokhale C, et al. Should NF2 mutation screening be undertaken in patients with an apparently isolated vestibular schwannoma?. Clin Genet 2007; 71:354.
Mohyuddin A, Neary WJ, Wallace A, et al. Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas. J Med Genet 2002; 39:315.
Kida Y, Kobayashi T, Tanaka T, Mori Y. Radiosurgery for bilateral neurinomas associated with neurofi bromatosis type 2. Surg Neurol 2000; 53:383.
Mathieu D, Kondziolka D, Flickinger JC, et al. Stereotactic radiosurgery for vestibular schwannomas in patients with neurofi bromatosis type 2: an analysis of tumor control, complications, and hearing preservation rates. Neurosurgery 2007; 60:460.
Roche PH, Regis J, Pellet W, et al. [Neurofi bromatosis type 2. Preliminary results of gamma knife radiosurgery of vestibular schwannomas]. Neurochirurgie 2000; 46:339.
Rowe JG, Radatz MW, Walton L, et al. Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofi bromatosis. J Neurol Neurosurg Psychiatry 2003; 74:1288.
Baser ME, Evans DG, Jackler RK, et al. Neurofi bromatosis 2, radiosurgery and malignant nervous system tumours. Br J Cancer 2000; 82:998.
Evans DG, Birch JM, Ramsden RT, et al. Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 2006; 43:289.
Balasubramaniam A, Shannon P, Hodaie M, et al. Glioblastoma multiforme after stereotactic radiotherapy for acoustic neuroma: Case report and review of the literature. Neuro Oncol 2007; 9:447.
Neff BA, Wiet RM, Lasak JM, et al. Cochlear implantation in the neurofi bromatosis type 2 patient: long-term follow-up. Laryngoscope 2007; 117:1069.
Wentworth S, Pinn M, Bourland JD, et al. Clinical experience with radiation therapy in the management of neurofi bromatosis-associated central nervous system tumors. Int J Radiat Oncol Biol Phys 2009; 73:208.
Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofi bromatosis type 2. Neuro Oncol 2010; 12:14.
Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofi bromatosis type 2. N Engl J Med 2009; 361:358.
Ruggieri M, Iannetti P, Polizzi A, et al. Earliest clinical manifestations and natural history of neurofi bromatosis type 2 (NF2) in childhood: a study of 24 patients. Neuropediatrics 2005; 36:21.
Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofi bromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol 1993; 52:106.
Evans DG, Huson SM, Donnai D, et al. A genetic study of type 2 neurofi bromatosis in the United Kingdom. I. Prevalence, mutation rate, fi tness, and confi rmation of maternal transmission effect on severity. J Med Genet 1992; 29:841.
Evans DG, Huson SM, Donnai D, et al. A genetic study of type 2 neurofi bromatosis in the United Kingdom. II. Guidelines for genetic counselling. J Med Genet 1992; 29:847.
Baser ME, Friedman JM, Aeschliman D, et al. Predictors of the risk of mortality in neurofi bromatosis 2. Am J Hum Genet 2002; 71:715.
Downloads
Published
2011-06-29
How to Cite
1.
กำเนิดศุภผล พ, เลียววิริยะกิจ น, หล่อวิทยา ว, สุขถมยา ว. Neurofi bromatosis type 2 Syndrome. J Thai Assn of Radiat Oncol [Internet]. 2011 Jun. 29 [cited 2024 Nov. 15];17(1):37-48. Available from: https://he01.tci-thaijo.org/index.php/jtaro/article/view/203481
Issue
Section
Original articles
License
บทความที่ได้รับการตีพิมพ์เป็นลิขสิทธิ์ของวารสารมะเร็งวิวัฒน์ ข้อความที่ปรากฏในบทความแต่ละเรื่องในวารสารวิชาการเล่มนี้เป็นความคิดเห็นส่วนตัวของผู้เขียนแต่ละท่านไม่เกี่ยวข้องกับ และบุคคลากรท่านอื่น ๆ ใน สมาคมฯ แต่อย่างใด ความรับผิดชอบองค์ประกอบทั้งหมดของบทความแต่ละเรื่องเป็นของผู้เขียนแต่ละท่าน หากมีความผิดพลาดใดๆ ผู้เขียนแต่ละท่านจะรับผิดชอบบทความของตนเองแต่ผู้เดียว
