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. 2017 Jan 3;88(1):87-92.
doi: 10.1212/WNL.0000000000003418. Epub 2016 Nov 16.

Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis

Miriam J Smith  1 , Naomi L Bowers  1 , Michael Bulman  1 , Carolyn Gokhale  1 , Andrew J Wallace  1 , Andrew T King  1 , Simon K L Lloyd  1 , Scott A Rutherford  1 , Charlotte L Hammerbeck-Ward  1 , Simon R Freeman  1 , D Gareth Evans  2
Affiliations

Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis

Miriam J Smith et al. Neurology. .

Erratum in

Abstract

Objective: To determine the specificity of the current clinical diagnostic criteria for neurofibromatosis type 2 (NF2) relative to the requirement for unilateral vestibular schwannoma (VS) and at least 2 other NF2-related tumors.

Methods: We interrogated our Manchester NF2 database, which contained 205 individuals meeting NF2 criteria who initially presented with a unilateral VS. Of these, 83 (40.7%) went on to develop a contralateral VS. We concentrated our genetic analysis on a group of 70 who initially fulfilled NF2 criteria with a unilateral vestibular schwannoma and at least 2 additional nonintradermal schwannomas.

Results: Overall, 5/70 (7%) individuals with unilateral VS and at least 2 other schwannomas had a pathogenic or likely pathogenic LZTR1 mutation. Twenty of the 70 subsequently developed bilateral disease. Of the remaining 50, 5 (10%) had a germline LZTR1 mutation, equivalent to the number (n = 5) with a germline NF2 mutation.

Conclusions: The most common etiology for unilateral VS and 2 additional NF2-associated tumors in this cohort was mosaic NF2. Germline LZTR1 and germline NF2 mutations were equally common in our cohort. This indicates that LZTR1 must be considered when making a diagnosis of NF2 in the presence of unilateral VS in individuals without a germline NF2 mutation.

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