NF2

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Neurofibromatosis type 2 (NF2) is a rare genetic condition that predisposes patients to tumors of the brain, spine and peripheral nerves (schwannomas, meningiomas, and ependymomas). Its incidence is one in every 33,000 to 40,000 individuals. The hallmark of NF2 is the development of tumors affecting the balance nerves in both ears (vestibular schwannomas). This condition is caused by a mutation in the NF2 gene on Chromosome 22 that produces the protein Merlin. 

Patients with NF2 usually develop symptoms in their teens or early adulthood. They frequently develop multiple simultaneous brain and spinal cord tumors. NF2 tumors may affect the nerves important for swallowing, speech, eye and facial movement, and facial sensation. 

Research and innovative clinical care are desperately needed to improve outcomes and quality of life for patients with NF2. Over the past 5 decades, physicians and researchers have been leaders in the field of NF2 research. Active efforts are underway to improve the care of patients with this condition. 

Past Research 

  • Natural History Study of NF2 – funded by Department of Defense. This study established the growth patterns of Vestibular Schwannomas in patients with NF2. This allows us to better understand how and when these tumors progress and when treatment is indicated 
  • Development of House Ear Institute NF cell lines. These in vitro cell lines are used around the world to test drug therapies for potential efficacy in NF
  • Development of the Auditory Brainstem Implant  
  • The development of the first central neural prosthesis for hearing restoration 
  • ABI technology is critical when the cochlear nerve is damaged by tumors in NF2
  • Surgical techniques for vestibular schwannomas (acoustic neuromas)  
  • Physicians at the House Institute have developed the primary surgical techniques for treating vestibular schwannomas in NF2 that are used throughout the world. These include the translabyrinthine approach and the middle fossa approach, which can be used as a hearing preservation strategy or for decompression alone  

Current Research 

  • Our goal is to better understand symptoms and improve care for patients with NF 
  • Specifically, we are systematically assessing symptoms that are important in NF, but have been typically overlooked by previous research studies. These include: 
    • Quality of life 
    • Hand function 
      • Peripheral neuropathy 
  • We are collecting tumor samples from patients with NF for future laboratory studies. This “tumor bank” will allow for genetic and molecular analysis of tumors by House Institute physicians and collaborating scientists 
  • We continue to analyze the outcomes of surgery and radiosurgery for patients with NF 

Events surrounding the condition  

  • Annual Children’s Tumor Foundation Conference (CTF) 
  • Local Shine a Light Walk benefiting CTF 
  • NF2 Symposium 

Our Team 

Publications List  

Bikhazi PH, Lalwani AK, Kim EJ, et al. Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma. Otolaryngol Head Neck Surg. 1998;119(1):1–6. doi:10.1016/S0194-5998(98)70166-4 

Bikhazi NB, Slattery WH 3rd, Lalwani AK, Jackler RK, Bikhazi PH, Brackmann DE. Familial occurrence of unilateral vestibular schwannoma. Laryngoscope. 1997;107(9):1176–1180. doi:10.1097/00005537-199709000-00004 

Black FO, Brackmann DE, Hitselberger WE, Purdy J. Preservation of auditory and vestibular function after surgical removal of bilateral vestibular schwannomas in a patient with neurofibromatosis type 2. Am J Otol. 1995;16(4):431–443. 

Blakeley JO, Evans DG, Adler J, et al. Consensus recommendations for current treatments and accelerating clinical trials for patients with neurofibromatosis type 2. Am J Med Genet A. 2012;158A(1):24–41. doi:10.1002/ajmg.a.34359 

Driscoll CL, Jackler RK, Pitts LH, Brackmann DE. Lesions of the internal auditory canal and cerebellopontine angle in an only hearing ear: is surgery ever advisable?. Am J Otol. 2000;21(4):573–581. 

Evans DG, Kalamarides M, Hunter-Schaedle K, et al. Consensus recommendations to accelerate clinical trials for neurofibromatosis type 2. Clin Cancer Res. 2009;15(16):5032–5039. doi:10.1158/1078-0432.CCR-08-3011 

Fisher LM, Doherty JK, Lev MH, Slattery WH. Concordance of bilateral vestibular schwannoma growth and hearing changes in neurofibromatosis 2: neurofibromatosis 2 natural history consortium. Otol Neurotol. 2009;30(6):835–841. doi:10.1097/MAO.0b013e3181b2364c 

Fisher LM, Doherty JK, Lev MH, Slattery WH 3rd. Distribution of nonvestibular cranial nerve schwannomas in neurofibromatosis 2 [published correction appears in Otol Neurotol. 2008 Sep;29(6):885]. Otol Neurotol. 2007;28(8):1083–1090. doi:10.1097/MAO.0b013e31815a8411 

Gadre AK, Kwartler JA, Brackmann DE, House WF, Hitselberger WE. Middle fossa decompression of the internal auditory canal in acoustic neuroma surgery: a therapeutic alternative. Laryngoscope. 1990;100(9):948–952. doi:10.1288/00005537-199009000-00007 

Harris GJ, Plotkin SR, Maccollin M, et al. Three-dimensional volumetrics for tracking vestibular schwannoma growth in neurofibromatosis type II. Neurosurgery. 2008;62(6):1314–1320. doi:10.1227/01.neu.0000333303.79931.83 

Hoa M, Slattery WH 3rd. Neurofibromatosis 2. Otolaryngol Clin North Am. 2012;45(2):315–viii. doi:10.1016/j.otc.2011.12.005 

Hung G, Faudoa R, Baser ME, et al. Neurofibromatosis 2 phenotypes and germ-line NF2 mutations determined by an RNA mismatch method and loss of heterozygosity analysis in NF2 schwannomas. Cancer Genet Cytogenet. 2000;118(2):167–168. doi:10.1016/s0165-4608(99)00201-0 

Harris GJ, Plotkin SR, Maccollin M, et al. Three-dimensional volumetrics for tracking vestibular schwannoma growth in neurofibromatosis type II. Neurosurgery. 2008;62(6):1314–1320. doi:10.1227/01.neu.0000333303.79931.83 

Hung G, Faudoa R, Li X, et al. Establishment of primary vestibular schwannoma cultures from neurofibromatosis type-2 patients. Int J Oncol. 1999;14(3):409–415. doi:10.3892/ijo.14.3.409 

Hung G, Li X, Faudoa R, et al. Establishment and characterization of a schwannoma cell line from a patient with neurofibromatosis 2. Int J Oncol. 2002;20(3):475–482. 

Mehrian-Shai R, Freedman S, Shams S, et al. Schwannomas exhibit distinct size-dependent gene-expression patterns. Future Oncol. 2015;11(12):1751–1758. doi:10.2217/fon.15.72 

Mehta GU, Huynh H, Lekovic GP. Peripheral nerve sheath tumors in Neurofibromatosis Type 2: Surgical and histopathologic features [published online ahead of print, 2019 Dec 23]. Clin Neurol Neurosurg. 2019;190:105649. doi:10.1016/j.clineuro.2019.105649 

Mehta GU, Feldman MJ, Wang H, Ding D, Chittiboina P. Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation. J Neurosurg. 2016;125(6):1469–1471. doi:10.3171/2015.11.JNS151766 

Merker VL, Bergner AL, Vranceanu AM, Muzikansky A, Slattery W 3rd, Plotkin SR. Health-related Quality of Life of Individuals With Neurofibromatosis Type 2: Results From the NF2 Natural History Study. Otol Neurotol. 2016;37(5):574–579. doi:10.1097/MAO.0000000000001019 

Montgomery BK, Alimchandani M, Mehta GU, et al. Tumors displaying hybrid schwannoma and neurofibroma features in patients with neurofibromatosis type 2. Clin Neuropathol. 2016;35(2):78–83. doi:10.5414/NP300895 

Otto SR, Brackmann DE, Hitselberger WE, Shannon RV, Kuchta J. Multichannel auditory brainstem implant: update on performance in 61 patients. J Neurosurg. 2002;96(6):1063–1071. doi:10.3171/jns.2002.96.6.1063 

Peng KA, Chen BS, Lorenz MB, et al. Revision Surgery for Vestibular Schwannomas. J Neurol Surg B Skull Base. 2018;79(6):528–532. doi:10.1055/s-0038-1635256 

Peng KA, Lorenz MB, Otto SR, Brackmann DE, Wilkinson EP. Cochlear implantation and auditory brainstem implantation in neurofibromatosis type 2. Laryngoscope. 2018;128(9):2163–2169. doi:10.1002/lary.27181 

Plotkin SR, Merker VL, Muzikansky A, Barker FG 2nd, Slattery W 3rd. Natural history of vestibular schwannoma growth and hearing decline in newly diagnosed neurofibromatosis type 2 patients. Otol Neurotol. 2014;35(1):e50–e56. doi:10.1097/MAO.0000000000000239 

Plotkin SR, Halpin C, Blakeley JO, et al. Suggested response criteria for phase II antitumor drug studies for neurofibromatosis type 2 related vestibular schwannoma. J Neurooncol. 2009;93(1):61–77. doi:10.1007/s11060-009-9867-7 

Roberts DS, Maurya R, Takemon Y, et al. Linked-read Sequencing Analysis Reveals Tumor-specific Genome Variation Landscapes in Neurofibromatosis Type 2 (NF2) Patients. Otol Neurotol. 2019;40(2):e150–e159. doi:10.1097/MAO.0000000000002096 

Roberts DS, Otto S, Chen B, et al. Tinnitus Suppression After Auditory Brainstem Implantation in Patients With Neurofibromatosis Type-2. Otol Neurotol. 2017;38(1):118–122. doi:10.1097/MAO.0000000000001230 

Roberts DS, Slattery WH, Chen BS, Otto SR, Schwartz MS, Lekovic GP. ‘Compassionate use’ protocol for auditory brainstem implantation in neurofibromatosis type 2: Early House Ear Institute experience. Cochlear Implants Int. 2017;18(1):57–62. doi:10.1080/14670100.2016.1258203 

Schwartz MS, Otto SR, Shannon RV, Hitselberger WE, Brackmann DE. Auditory brainstem implants. Neurotherapeutics. 2008;5(1):128–136. doi:10.1016/j.nurt.2007.10.068 

Slattery WH. Neurofibromatosis type 2. Otolaryngol Clin North Am. 2015;48(3):443–460. doi:10.1016/j.otc.2015.02.005 

Slattery WH 3rd, Fisher LM, Hitselberger W, Friedman RA, Brackmann DE. Hearing preservation surgery for neurofibromatosis Type 2-related vestibular schwannoma in pediatric patients. J Neurosurg. 2007;106(4 Suppl):255–260. doi:10.3171/ped.2007.106.4.255 

Slattery WH 3rd, Fisher LM, Iqbal Z, Oppenhiemer M. Vestibular schwannoma growth rates in neurofibromatosis type 2 natural history consortium subjects. Otol Neurotol. 2004;25(5):811–817. doi:10.1097/00129492-200409000-00027 

Slattery WH 3rd, Brackmann DE, Hitselberger W. Hearing preservation in neurofibromatosis type 2. Am J Otol. 1998;19(5):638–643. 

Slattery WH, Lev MH, Fisher LM, et al. MRI evaluation of neurofibromatosis 2 patients: a standardized approach for accuracy in interpretation. Otol Neurotol. 2005;26(4):733–740. doi:10.1097/01.mao.0000169048.15889.80 

Toren A, Reichardt JK, Andalibi A, et al. Novel age-dependent targets in vestibular schwannomas. Hum Genomics. 2014;8(1):10. Published 2014 Jun 30. doi:10.1186/1479-7364-8-10