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Child's Nervous System

, Volume 32, Issue 12, pp 2403–2413 | Cite as

Pediatric neurofibromatosis type 2: clinical and molecular presentation, management of vestibular schwannomas, and hearing rehabilitation

  • Nicolas -Xavier BonneEmail author
  • Rabih Aboukais
  • Marc Baroncini
  • Audrey Hochart
  • Pierre Leblond
  • Franck Broly
  • Frédérique Dubrulle
  • Jean-Paul Lejeune
  • Christophe Vincent
Original Paper

Abstract

Objective

This study aims to describe the clinical and molecular presentation of pediatric neurofibromatosis type 2 (NF2) and the subsequent management of vestibular schwannomas (VS) and hearing rehabilitation.

Methods

This is a single-center retrospective study of neurofibromatosis type 2 diagnosed before the age of 18 years old from 1997. Natural history of vestibular schwannomas and surgical outcomes were evaluated using volumetric MRI, hearing, and facial nerve assessment. Patients included in chemotherapy protocols were excluded.

Results

From a database of 80 patients followed up for NF2 on a regular basis, 25 patients were eligible (11 sporadic cases, 14 inherited in five families). The mean age at diagnosis was 11.6 years old. The average clinical follow-up was 6.5 years. NF2 mutation was identified in 81 % of the probands. The average growth rate based on the maximum linear diameter (DGR) was 1.68 mm/year (n = 33, average follow-up 4.22 years) and 545 mm3/year in volumetric assessment (VGR) for VS larger than 1 cm (n = 21, average follow-up 3.4 years). In unoperated ears, hearing was stable in about 50 % of ears. The mean change in dB HL was 9.5 dB/year for pure-tone average and 3.5 for speech-recognition threshold (n = 34, 5.5 years 1–12). Eight children required removal through a translabyrinthine approach (mean follow-up was 4.5 years), six patients were operated on for hearing preservation (mean postoperative follow-up 4.3 years). Six patients were eligible for hearing rehabilitation with cochlear implantation (I), and five received placement of an auditory brainstem implant.

Conclusion

Early diagnosis and treatment of small growing VS should be carefully discussed considering familial history and possible rehabilitation with a CI.

Keywords

Neurofibromatosis type 2 Vestibular schwannoma Middle fossa Hearing préservation Auditory brainstem implant 

Abbreviations

LOH

Loss of heterozygocity

NF2

Neurofibromatosis type 2

PSC

Posterior subcapsular cataract

PTA

Pure-tone average

SDS

Speech-discrimination score

SRT

Speech-recognition threshold

VS

Vestibular schwannoma

Notes

Acknowledgments

Authors’ contributions

Dr. Nicolas-Xavier Bonne conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted. Dr. Rabih Aboukais helped in data collection and approved the final manuscript as submitted. Dr. Marc Baroncini participated in data collection, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr. Audrey Hochart critically reviewed the manuscript and approved the final manuscript as submitted. Dr. Pierre Leblond critically reviewed the manuscript and approved the final manuscript as submitted. Dr. Franck Broly critically reviewed the manuscript and approved the final manuscript as submitted. Dr. Frederique Dubrulle critically reviewed the manuscript and approved the final manuscript as submitted. Pr. Jean-Paul Lejeune critically reviewed the manuscript and approved the final manuscript as submitted. Pr. Christophe Vincent supervised the work, critically reviewed the manuscript, and approved the final manuscript as submitted.

Compliance with ethical standards

Funding sources

No external funding was secured for this study.

Financial disclosure

All authors have no financial relationships relevant to this article to disclose.

Conflict of interest

All authors have no conflicts of interest to disclose.

References

  1. 1.
    Evans DGR (2009) Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis 4:16. doi: 10.1186/1750-1172-4-16 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wilding A, Ingham SL, Lalloo F, et al. (2012) Life expectancy in hereditary cancer predisposing diseases: an observational study. J Med Genet 49:264–269. doi: 10.1136/jmedgenet-2011-100562 CrossRefPubMedGoogle Scholar
  3. 3.
    Otsuka G, Saito K, Nagatani T, Yoshida J (2003) Age at symptom onset and long-term survival in patients with neurofibromatosis type 2. J Neurosurg 99:480–483. doi: 10.3171/jns.2003.99.3.0480 CrossRefPubMedGoogle Scholar
  4. 4.
    Evans DG, Birch JM, Ramsden RT (1999) Paediatric presentation of type 2 neurofibromatosis. Arch Dis Child 81:496–499CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Martuza RL, Ojemann RG (1982) Bilateral acoustic neuromas: clinical aspects, pathogenesis, and treatment. Neurosurgery 10:1–12CrossRefPubMedGoogle Scholar
  6. 6.
    Rouleau GA, Seizinger BR, Wertelecki W, et al. (1990) Flanking markers bracket the neurofibromatosis type 2 (NF2) gene on chromosome 22. Am J Hum Genet 46:323–328PubMedPubMedCentralGoogle Scholar
  7. 7.
    Trofatter JA, MacCollin MM, Rutter JL, et al. (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 75:826CrossRefPubMedGoogle Scholar
  8. 8.
    Rouleau GA, Merel P, Lutchman M, et al. (1993) Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:515–521. doi: 10.1038/363515a0 CrossRefPubMedGoogle Scholar
  9. 9.
    Knudson AG (1974) Heredity and human cancer. Am J Pathol 77:77–84PubMedPubMedCentralGoogle Scholar
  10. 10.
    Knudson AG (1976) Genetics and the etiology of childhood cancer. Pediatr Res 10:513–517. doi: 10.1203/00006450-197605000-00001 CrossRefPubMedGoogle Scholar
  11. 11.
    Baser ME, Evans DGR, Gutmann DH (2003) Neurofibromatosis 2. Curr Opin Neurol 16:27–33. doi: 10.1097/01.wco.0000053583.70044.ab CrossRefPubMedGoogle Scholar
  12. 12.
    Evans DGR, Ramsden RT, Shenton A, et al. (2007) 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 44:424–428. doi: 10.1136/jmg.2006.047753 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Baser ME, Mautner VF, Ragge NK, et al. (1996) Presymptomatic diagnosis of neurofibromatosis 2 using linked genetic markers, neuroimaging, and ocular examinations. Neurology 47:1269–1277CrossRefPubMedGoogle Scholar
  14. 14.
    Evans DG, Newton V, Neary W, et al. (2000) Use of MRI and audiological tests in presymptomatic diagnosis of type 2 neurofibromatosis (NF2. J Med Genet 37:944–947CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Harsh GR, MacCollin M, McKenna MJ, et al. (1995) Molecular genetic screening for children at risk of neurofibromatosis 2. Arch Otolaryngol Head Neck Surg 121:590–591CrossRefPubMedGoogle Scholar
  16. 16.
    Sestini R, Bacci C, Provenzano A, et al. (2008) Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas. Hum Mutat 29:227–231. doi: 10.1002/humu.20679 CrossRefPubMedGoogle Scholar
  17. 17.
    Piotrowski A, Xie J, Liu YF, et al. (2014) Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nat Genet 46:182–187. doi: 10.1038/ng.2855 CrossRefPubMedGoogle Scholar
  18. 18.
    Parry DM, Eldridge R, Kaiser-Kupfer MI, et al. (1994) Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet 52:450–461. doi: 10.1002/ajmg.1320520411 CrossRefPubMedGoogle Scholar
  19. 19.
    Mautner VF, Tatagiba M, Guthoff R, et al. (1993) Neurofibromatosis 2 in the pediatric age group. Neurosurgery 33:92–96CrossRefPubMedGoogle Scholar
  20. 20.
    Ruggieri M, Iannetti P, Polizzi A, et al. (2005) Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: a study of 24 patients. Neuropediatrics 36:21–34. doi: 10.1055/s-2005-837581 CrossRefPubMedGoogle Scholar
  21. 21.
    Ruggieri M, Gabriele AL, Polizzi A, et al. (2013) Natural history of neurofibromatosis type 2 with onset before the age of 1 year. Neurogenetics 14:89–98. doi: 10.1007/s10048-013-0354-0 CrossRefPubMedGoogle Scholar
  22. 22.
    Slattery WH 3rd, Fisher LM, Hitselberger W, et al. (2007) Hearing preservation surgery for neurofibromatosis type 2-related vestibular schwannoma in pediatric patients. J Neurosurg 106:255–260. doi: 10.3171/ped.2007.106.4.255 CrossRefPubMedGoogle Scholar
  23. 23.
    Otto SR, Brackmann DE, Hitselberger W (2004) Auditory brainstem implantation in 12- to 18-year-olds. Arch Otolaryngol Head Neck Surg 130:656–659. doi: 10.1001/archotol.130.5.656 CrossRefPubMedGoogle Scholar
  24. 24.
    Cunningham CD, Friedman RA, Brackmann DE, et al. (2005) Neurotologic skull base surgery in pediatric patients. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 26:231–236CrossRefGoogle Scholar
  25. 25.
    MacNally SP, Rutherford SA, King AT, et al. (2009) Outcome from surgery for vestibular schwannomas in children. Br J Neurosurg 23:226–231. doi: 10.1080/02688690902968844 CrossRefPubMedGoogle Scholar
  26. 26.
    Niemczyk K, Dubrulle F, Vaneecloo FM, et al. (2002) Clinical implications of acoustic neuromas growth rate in volumetric study. Ann Oto-Laryngol Chir Cervico Faciale Bull Société Oto-Laryngol Hôpitaux Paris 119:259–263Google Scholar
  27. 27.
    Niemczyk K, Vaneecloo FM, Lemaitre L, et al. (1999) The growth of acoustic neuromas in volumetric radiologic assessment. Am J Otol 20:244–248PubMedGoogle Scholar
  28. 28.
    Dubrulle F, Ernst O, Vincent C, et al. (2000) Cochlear fossa enhancement at MR evaluation of vestibular schwannoma: correlation with success at hearing-preservation surgery. Radiology 215:458–462. doi: 10.1148/radiology.215.2.r00ma20458 CrossRefPubMedGoogle Scholar
  29. 29.
    Friedman RA, Goddard JC, Wilkinson EP, et al. (2011) Hearing preservation with the middle cranial fossa approach for neurofibromatosis type 2. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 32:1530–1537. doi: 10.1097/MAO.0b013e3182355855 CrossRefGoogle Scholar
  30. 30.
    Brackmann DE, Fayad JN, Slattery WH 3rd, et al. (2001) Early proactive management of vestibular schwannomas in neurofibromatosis type 2. Neurosurgery 49:274–280 discussion 280–283PubMedGoogle Scholar
  31. 31.
    Goddard JC, Schwartz MS, Friedman RA (2010) Fundal fluid as a predictor of hearing preservation in the middle cranial fossa approach for vestibular schwannoma. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 31:1128–1134. doi: 10.1097/MAO.0b013e3181e8fc3f CrossRefGoogle Scholar
  32. 32.
    Vincent C, Bonne N-X, Guérin C, et al. (2012) Middle fossa approach for resection of vestibular schwannoma: impact of cochlear fossa extension and auditory monitoring on hearing preservation. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 33:849–852. doi: 10.1097/MAO.0b013e318254ede3 CrossRefGoogle Scholar
  33. 33.
    Slattery WH, Hoa M, Bonne N, et al. (2011) Middle fossa decompression for hearing preservation: a review of institutional results and indications. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 32:1017–1024. doi: 10.1097/MAO.0b013e3182267eb7 CrossRefGoogle Scholar
  34. 34.
    Tringali S, Ferber-Viart C, Fuchsmann C, et al. (2010) Hearing preservation in retrosigmoid approach of small vestibular schwannomas: prognostic value of the degree of internal auditory canal filling. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 31:1469–1472Google Scholar
  35. 35.
    Samii M (1995) Hearing preservation in bilateral acoustic neurinomas. Br J Neurosurg 9:413–424CrossRefPubMedGoogle Scholar
  36. 36.
    Samii M, Matthies C, Tatagiba M (1997) Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2. Neurosurgery 40:696–705 discussion 705–706CrossRefPubMedGoogle Scholar
  37. 37.
    Jääskeläinen J, Paetau A, Pyykkö I, et al. (1994) Interface between the facial nerve and large acoustic neurinomas. Immunohistochemical study of the cleavage plane in NF2 and non-NF2 cases. J Neurosurg 80:541–547. doi: 10.3171/jns.1994.80.3.0541 CrossRefPubMedGoogle Scholar
  38. 38.
    Nam S-I, Linthicum FH, Merchant SN (2011) Temporal bone histopathology in neurofibromatosis type 2. Laryngoscope 121:1548–1554. doi: 10.1002/lary.21822 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Cueva RA, Thedinger BA, Harris JP, Glasscock ME (1992) Electrical promontory stimulation in patients with intact cochlear nerve and anacusis following acoustic neuroma surgery. Laryngoscope 102:1220–1224. doi: 10.1288/00005537-199211000-00003 CrossRefPubMedGoogle Scholar
  40. 40.
    Tran Ba Huy P, Kania R, Frachet B, et al. (2009) Auditory rehabilitation with cochlear implantation in patients with neurofibromatosis type 2. Acta Otolaryngol (Stockh) 129:971–975. doi: 10.1080/00016480802510202 CrossRefGoogle Scholar
  41. 41.
    Vincenti V, Pasanisi E, Guida M, et al. (2008) Hearing rehabilitation in neurofibromatosis type 2 patients: cochlear versus auditory brainstem implantation. Audiol Neurootol 13:273–280. doi: 10.1159/000115437 CrossRefPubMedGoogle Scholar
  42. 42.
    Neff BA, Wiet RM, Lasak JM, et al. (2007) Cochlear implantation in the neurofibromatosis type 2 patient: long-term follow-up. Laryngoscope 117:1069–1072. doi: 10.1097/MLG.0b013e31804b1ae7 CrossRefPubMedGoogle Scholar
  43. 43.
    Trotter MI, Briggs RJS (2010) Cochlear implantation in neurofibromatosis type 2 after radiation therapy. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 31:216–219. doi: 10.1097/MAO.0b013e3181c348e7 CrossRefGoogle Scholar
  44. 44.
    Roehm PC, Mallen-St Clair J, Jethanamest D, et al. (2011) Auditory rehabilitation of patients with neurofibromatosis type 2 by using cochlear implants. J Neurosurg 115:827–834. doi: 10.3171/2011.5.JNS101929 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Lustig LR, Yeagle J, Driscoll CLW, et al. (2006) Cochlear implantation in patients with neurofibromatosis type 2 and bilateral vestibular schwannoma. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 27:512–518. doi: 10.1097/01.mao.0000217351.86925.51 Google Scholar
  46. 46.
    Vincent C, Zini C, Gandolfi A, et al. (2002) Results of the MXM Digisonic auditory brainstem implant clinical trials in Europe. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 23:56–60CrossRefGoogle Scholar
  47. 47.
    Colletti V, Shannon RV, Carner M, et al. (2010) Complications in auditory brainstem implant surgery in adults and children. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 31:558–564. doi: 10.1097/MAO.0b013e3181db7055 Google Scholar
  48. 48.
    Baser ME, Evans DG, Jackler RK, et al. (2000) Neurofibromatosis 2, radiosurgery and malignant nervous system tumours. Br J Cancer 82:998. doi: 10.1054/bjoc.1999.1030 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Evans DGR (2009) Neurofibromatosis 2 [bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med Off J Am Coll Med Genet 11:599–610. doi: 10.1097/GIM.0b013e3181ac9a27 Google Scholar
  50. 50.
    Choi CYH, Soltys SG, Gibbs IC, et al. (2011) Stereotactic radiosurgery of cranial nonvestibular schwannomas: results of single- and multisession radiosurgery. Neurosurgery 68:1200–1208 . doi: 10.1227/NEU.0b013e31820c0474discussion 1208CrossRefPubMedGoogle Scholar
  51. 51.
    Hochart A, Gaillard V, Baroncini M, et al. (2015) Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2. J Neuro-Oncol 124:229–236. doi: 10.1007/s11060-015-1828-8 CrossRefGoogle Scholar
  52. 52.
    Giovannini M, Bonne N-X, Vitte J, et al. (2014) mTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma. Neuro-Oncol. doi: 10.1093/neuonc/not242 PubMedPubMedCentralGoogle Scholar
  53. 53.
    Karajannis MA, Legault G, Hagiwara M, et al. (2014) Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro-Oncol 16:292–297. doi: 10.1093/neuonc/not150 CrossRefPubMedGoogle Scholar
  54. 54.
    Goutagny S, Raymond E, Esposito-Farese M, et al. (2015) Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. J Neuro-Oncol 122:313–320. doi: 10.1007/s11060-014-1710-0 CrossRefGoogle Scholar
  55. 55.
    Ruggieri M, Praticò AD, Evans DG (2015) Diagnosis, management, and new therapeutic options in childhood Neurofibromatosis type 2 and related forms. Semin Pediatr Neurol 22:240–258. doi: 10.1016/j.spen.2015.10.008 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Nicolas -Xavier Bonne
    • 1
    Email author
  • Rabih Aboukais
    • 2
  • Marc Baroncini
    • 2
  • Audrey Hochart
    • 3
  • Pierre Leblond
    • 3
  • Franck Broly
    • 4
    • 5
  • Frédérique Dubrulle
    • 6
  • Jean-Paul Lejeune
    • 2
  • Christophe Vincent
    • 1
  1. 1.Department of Otology and NeurotologyCHRU de LilleLilleFrance
  2. 2.Department of NeurosurgeryCHRU de LilleLille CedexFrance
  3. 3.Department of Pediatric OncologyCentre Oscar LambretLilleFrance
  4. 4.Department of GeneticCHRU de LilleLille CedexFrance
  5. 5.Service de Toxicologie, GénopathiesCHRU LilleLilleFrance
  6. 6.Department of Radiology, Hôpital HuriezCHRU LilleLilleFrance

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