Neurofibromatosis type 2 (NF2) is a rare genetic syndrome characterized by bilateral vestibular schwannomas and other tumors. It has an average age of diagnosis of 25 years. Care requires a multidisciplinary team approach due to the variety of tumors involved. Management may include observation, surgery, radiation, or drug therapies targeting tumor growth pathways.

1. NEUROFIBROMATOSIS
TYPE II
Ade Wijaya, MD – November 2018

2. Outline:
• Introduction
• Epidemiology
• Diagnostic Criteria
• Diagnosis
• Clinical Features
• Management
• Summary

3. Introduction
• Rare syndrome
• Hearing loss as presenting symptom
• Invasive, requiring a multispecialist team approach
• Chromosome 22
Slattery WH. Neurofibromatosis type 2. Otolaryngologic Clinics of North America. 2015 Jun 1;48(3):443-60.

4. Epidemiology
• The average age of diagnosis of NF2 is 25 years
• The average delay of diagnosis is 7 years
• No gender or ethnicity difference
• Epidemiologic studies place the incidence of NF2 between 1 in 33,000 live births and 1 in 87,410
live births
Shelton C, Brackmann DE, House WF. Middle fossa approach. In: Brackmann DE, Shelton C, Arriaga MA, editors. Otologic surgery. 3rd edition. Philadelphia: Elsevier; 2010. p. 581–9.
Antinheimo J, Sankila R, Carpen O, et al. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology 2000;54:71–6.
Evans DG, Howard E, Giblin C, et al. Birth incidence and prevalence of tumorprone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 2010;152A:327–32.

5. Diagnostic Criteria

6. Diagnosis
• A high-quality MRI scan performed with thin cuts through the internal auditory canals (IAC).
• Spine imaging
• Family history and genetic testing
Slattery WH. Neurofibromatosis type 2. Otolaryngologic Clinics of North America. 2015 Jun 1;48(3):443-60.

7. Clinical Features
Slattery WH. Neurofibromatosis 2 in otologic surgery. In: Brackmann DE, Shelton C, Arriaga MA, editors. Philadelphia: Elsevier; 2010. p. 691–701

8. Other Tumor Type in NF2
Slattery WH. Neurofibromatosis 2 in otologic surgery. In: Brackmann DE, Shelton C, Arriaga MA, editors. Philadelphia: Elsevier; 2010. p. 691–701

9. Management
• Observation
• Surgical
• Hearing preservation
• Auditory brainstem implant
• Cochlear implant
• Stereotactic irradiation
• Drug therapy
Slattery WH. Neurofibromatosis type 2. Otolaryngologic Clinics of North America. 2015 Jun 1;48(3):443-60.

10. Management (Drug Therapy)
• Target multiple intracellular signaling pathways that interact with the NF2 protein, including the
phosphatidylinositol 3 kinase/Akt, Raf/MEK/ERK, and mTOR pathways as well as integrin/focal
adhesion kinase/Src/Ras signaling cascades, platelet-derived growth factor receptor beta, and
vascular endothelial growth factor (VEGF) pathways.
• Erlotinib, lapatinib, and bevacizumab, avastin, rapamycin.
Wong HK, Lahdenranta J, Kamoun WS, et al. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosisrelated tumors. Cancer Res 010;70(9):3483–93.
Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med 2009;361(4):358–67.
Plotkin SR, Singh MA, O’Donnell CC, et al. Audiologic and radiographic response of NF2-related vestibular schwannoma to erlotinib therapy. Nat Clin Pract Oncol 2008;5(8):487–91.
Plotkin SR, Halpin C, McKenna MJ, et al. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol 2010;31(7):1135–43.
Evans DG. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis 2009;4:16.

11. Summary
• Care of patients with NF2 requires knowledge of all tumors and symptoms involved with the
disorder.
• Bilateral schwanomas
• Multidisciplinary approach