Download Cancer Prone Disease Section Neurofibromatosis type 2 (NF2) in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Cancer Prone Disease Section
Mini Review
Neurofibromatosis type 2 (NF2)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Published in Atlas Database: March 1998
Online updated version is available from: http://AtlasGeneticsOncology.org/Kprones/NF2Kpr10007.html
DOI: 10.4267/2042/37447
This article is an update of: Huret JL. Neurofibromatosis type 2 (NF2). Atlas Genet Cytogenet Oncol Haematol.1997;1(1):37-38.
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology
prognosis; patients with the Wishart severe form
usually do not survive past 50 yrs.
Identity
Other names: 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).
Cytogenetics
Inborn condition
Normal.
Cancer cytogenetics
Chromosome 22 loss is very frequent both in sporadic
and in NF2 schwannomas and meningiomas.
Clinics
Genes involved and Proteins
NF2 is an hamartoneoplastic syndrome; hamartomas
are localized tissue proliferations with faulty
differentiation and mixture of component tissues; they
are heritable malformations that have a potential
towards neoplasia.
NF2 (neurofibromin 2)
Location: 22q12
DNA/RNA
Description: 16 exons.
Protein
Description: contains a membrane binding domain and
a helix binding to actin of the cytoskeleton.
Expression: wide.
Function: membrane-cytoskeleton anchor; should be a
tumour suppressor.
Homology
Band 4.1 family.
Mutations
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
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 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 give them a grave
Atlas Genet Cytogenet Oncol Haematol. 1998;2(3)
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Neurofibromatosis type 2 (NF2)
Huret JL
and meningiomas are in accordance with the two-hit
model for neoplasia.
Marineau C, Mérel P, Rouleau GA, Thomas G. Le gène de la
neurofibromatose de type 2. Médecine/sciences 1995; 11:3542. (Review). French.
References
Parry DM, MacCollin MM, Kaiser-Kupfer MI, Pulaski K,
Nicholson HS, Bolesta M, Eldridge R, Gusella JF. Germ-line
mutations in the neurofibromatosis 2 gene: correlations with
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Ruttledge MH, Andermann AA, Phelan CM, Claudio JO, Han
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Rouleau GA, Mérel P, Lutchman M, Sanson M, Zucman J,
Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C,
Plougastel B, et al. Alteration in a new gene encoding a
putative membrane-organizing protein causes neurofibromatosis type 2. Nature 1993 Jun 10;363(6429):515-21.
This article should be referenced as such:
Parry DM, Eldridge R, Kaiser-Kupfer MI, Bouzas EA, Pikus A,
Patronas N. Neurofibromatosis 2 (NF2): clinical characteristics
of 63 affected individuals and clinical evidence for
heterogeneity. Am J Med Genet 1994 Oct 1;52(4):450-61.
Huret JL. Neurofibromatosis type 2 (NF2). Atlas Genet
Cytogenet Oncol Haematol.1998;2(3):109-110.
Evans DG, Bourn D, Wallace A, Ramsden RT, Mitchell JD,
Strachan T. Diagnostic issues in a family with late onset type 2
neurofibromatosis. J Med Genet 1995 Jun;32(6):470-4.
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