Characterization of early onset neurofibromatosis type 2

Published:February 15, 2013DOI:


      Neurofibromatosis type 2 (NF2) is an autosomal dominant multiple neoplasia syndrome of the central nervous system. The aim of the present study was to characterize the clinical course of early onset NF2. The specific Japanese disease registry for NF2 in 2010 was analyzed retrospectively. The male:female ratio for the 312 patients identified in the database was 1:1.29. The median age at onset was 25 years (range 2–76 years), with 31.3% of patients exhibiting symptoms at <20 years of age. Patients with an age at onset of <20 years were found to have more frequent spinal cord and extravestibular cranial nerve involvement, cutaneous signs, and convulsions than patients with a later age at onset. Of patients younger than 18 years of age, half did not exhibit hearing problems; in contrast, they frequently had other cranial nerve schwannomas, cranial meningioma, spinal cord tumors, and subcutaneous schwannoma. There were weak but significant positive correlations between symptomatic periods and disability scores in patients with an age of onset of ⩾20 years (R = 0.225; P < 0.01) and those with an earlier age of onset (R= 0.306; P< 0.01). Although there were no significant differences in disability scores between genders or patients with an age at onset of <20 versus ⩾20 years, patients with an earlier age at onset had significantly higher disability scores for spinal symptoms than patients with an age at onset of ⩾20 years. Atypical extravestibular presentation is common in early onset NF2, with more prominent spinal symptoms.


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        • Trofatter J.A.
        • MacCollin M.M.
        • Rutter J.L.
        • Murrell J.R.
        • Duyao M.P.
        • Parry D.M.
        • et al.
        A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.
        Cell. 1993; 72: 791-800
        • Rouleau G.A.
        • Merel P.
        • Lutchman M.
        • Sanson M.
        • Zucman J.
        • Marineau C.
        • et al.
        Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.
        Nature. 1993; 363: 515-521
        • Evans D.G.
        • Howard E.
        • Giblin C.
        • Clancy T.
        • Spencer H.
        • Huson S.M.
        • et al.
        Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service.
        Am J Med Genet A. 2010; 152: 327-332
        • Evans D.G.
        • Huson S.M.
        • Donnai D.
        • Neary W.
        • Blair V.
        • Newton V.
        • et al.
        A clinical study of type 2 neurofibromatosis.
        Q J Med. 1992; 84: 603-618
        • Parry D.M.
        • Eldridge R.
        • Kaiser-Kupfer M.I.
        • Bouzas E.A.
        • Pikus A.
        • Patronas N.
        Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.
        Am J Med Genet. 1994; 52: 450-461
        • The Consensus Development Panel
        National Institutes of Health Consensus Development Conference statement on Acoustic Neuroma, December 11–13, 1991.
        Arch Neurol. 1994; 51: 201-207
        • Evans D.G.
        • 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: 93-97
        • Evans D.G.
        • Birch J.M.
        • Ramsden R.T.
        Paediatric presentation of type 2 neurofibromatosis.
        Arch Dis Child. 1999; 81: 496-499
        • Kotecha R.S.
        • Pascoe E.M.
        • Rushing E.J.
        • Rorke-Adams L.B.
        • Zwerdling T.
        • Gao X.
        • et al.
        Meningiomas in children and adolescents: a meta-analysis of individual patient data.
        Lancet Oncol. 2011; 12: 1229-1239
        • 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
        • MacCollin M.
        • Mautner V.F.
        The diagnosis and management of neurofibromatosis 2 in childhood.
        Semin Pediatr Neurol. 1998; 5: 243-252
        • Mautner V.F.
        • Tatagiba M.
        • Guthoff R.
        • Samii M.
        • Pulst S.M.
        • Hoffman H.J.
        • et al.
        Neurofibromatosis 2 in the pediatric age group.
        Neurosurgery. 1993; 33: 92-96
        • 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: 480-483
        • Baser M.E.
        • Friedman J.M.
        • Aeschliman D.
        • Joe H.
        • Wallace A.J.
        • Ramsden R.T.
        • et al.
        Predictors of the risk of mortality in neurofibromatosis 2.
        Am J Hum Genet. 2002; 71: 715-723