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Neurofibromatosis type 2

Author
D Gareth Evans, MD, FRCP
Section Editors
Jay S Loeffler, MD
Patrick Y Wen, MD
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

Neurofibromatosis type 2 (NF2) is a dominantly inherited syndrome that predisposes individuals to multiple tumors of the nervous system [1-3]. The most common of these are bilateral vestibular schwannomas; intracranial and spinal meningiomas and spine tumors, including intrinsic ependymomas, are also a prominent component of this condition. Mutations in the NF2 gene, which produces merlin, a tumor suppressor, are responsible for this syndrome.

The molecular pathogenesis, clinical features, diagnosis, and patient management of NF2 are reviewed here. Neurofibromatosis type 1 (NF1) (von Recklinghausen's disease) and schwannomatosis are discussed separately. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis" and "Schwannomatosis".)

MOLECULAR PATHOGENESIS

NF2 gene — Neurofibromatosis type 2 (NF2) is consistently linked with abnormalities of the NF2 gene, which is located on chromosome 22 [4]. The NF2 gene produces merlin, also known as schwannomin, a cell membrane-related protein that acts as a tumor suppressor [5,6].

Detailed molecular testing will identify an abnormality in NF2 in over 93 percent of families with multiple members affected with NF2 [7]. For individuals thought to harbor a new de novo mutation, somatic mosaicism may prevent the molecular diagnosis from being established unless tumor tissue is analyzed [7-10].

The development of schwannomas and other tumors requires inactivation of both NF2 alleles, since tumors only develop in cells that have lost function of their normal NF2 allele. Individuals with NF2 may inherit an abnormal NF2 allele from a parent. Alternatively, a de novo mutation may take place after fertilization, resulting in a mosaic expression of two cell lines.

                          

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Literature review current through: Nov 2016. | This topic last updated: Wed Aug 03 00:00:00 GMT+00:00 2016.
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References
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