Neurofibromatosis type 2 (NF2)

2001-02-01   James F Gusella  

Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA

Identity

Name

Neurofibromatosis type 2 (NF2)

Alias

Central neurofibromatosis , Bilateral acoustic neurofibromatosis , Bilateral acoustic neurinoma , Bilateral acoustic schwannomas

Inheritance

autosomal dominant with almost complete penetrance; frequency is 3\/105 newborns; neomutation represent 50% of cases; variable expressivity from mild disease through life (Gardner type) to severe condition at young age (Wishart type: with more than 3 tumours)

Omim

101000

Mesh

D009464;D016518

Orphanet

637 Neurofibromatosis type 2

Umls

C0027832;C0027859

Clinics

Note

NF2 is an hamartoneoplastic syndrome; hamartomas are localized tissue proliferations with faulty differenciation and mixture of component tissues; they are heritable malformations that have a potential towards neoplasia

Phenotype and clinics

  • bilateral vestibular (8th cranial pair) schwannomas; other central or peripheral nerve schwannomas; meningiomas; ependymomas.
  • hearing loss (average age 20 yrs), tinnitus, imbalance, headache, cataract in 50%, facial paralysis.
  • café-au-lait spots and cutaneous and peripheral neurofibromas may be present, but far less extensively than in neurofibromatosis type 1

    • Neoplastic risk

    NF2 cases represent about 5 % of schwannomas and meningiomas (i.e. risk increased by 2000), appearing at the age of 20, while they are found in the general population at the age of 50 and over

    Prognosis

    these tumours are usually benign, but their location within the central nervous system gives them a grave prognosis; patients with the Wishart severe form usually do not survive past 50 yrs

    Cytogenetics

    Inborn condition

    normal

    Cancer cytog

    chromosome 22 loss is very frequent both in sporadic and in NF2 schwannomas and meningiomas

    Genes involved and Proteins

    Description

    17 exons (1-15, 17 constitutive, 16 alternatively spliced)

    Expression

    wide

    Function

    membrane-cytoskeleton anchor; tumour suppressor

    Homology

    band 4.1 family , ezrin, radixin, moesin

    Germinal

    germ-line mutations in NF2 patients lead to protein truncation; splice-site or missense mutations are also found; phenotype-genotype correlations are observed (i.e. that severe phenotype are found in cases with protein truncations rather than those with amino acid substitution)

    Somatic

    mutation and allele loss events in tumours in neurofibromatosis type 2 and in sporadic schwannomas and meningiomas are in accordance with the two-hit model for neoplasia

    To be noted

    Hgmd

    120232

    Databases

    http:\/\/www.geneclinics.org\/profiles\/nf2 Neurofibromatosis Type 2 - GeneClinics

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    94252291998Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane.Deguen B et al
    76664001995Diagnostic issues in a family with late onset type 2 neurofibromatosis.Evans DG et al
    108871562000Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.Giovannini M et al
    102143501999Merlin: the neurofibromatosis 2 tumor suppressor.Gusella JF et al
    110855922000The parental origin of new mutations in neurofibromatosis 2.Kluwe L et al
    109921632000Advances in neurofibromatosis 2 (NF2): a workshop report.Lim DJ et al
    91713701997The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation.McClatchey AI et al
    77477581994Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.Parry DM et al
    87518531996Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities.Parry DM et al
    83799981993Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.Rouleau GA et al
    87559191996Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.Ruttledge MH et al
    84536691993A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.Trofatter JA et al