Abstract

Background: NF2 is almost unique amongst inherited disorders in the frequency of mosaicism in the first affected generation. However, the implications of this on transmission risks have not been fully elucidated.

Methods: We have analysed our expanded database of 460 NF2 families and 704 affected individuals for mosaicism and transmission risks to offspring.

Results: we have identified 64 mosaic patients with a projected mosaicism rate of 33% for sporadic classical NF2 with bilateral Vestibular schwannoma at presentation and 60% for those presenting unilaterally. Offspring risks can be radically reduced on the basis of a sensitive mutation analysis of blood DNA including MLPA (detects 15% of all mutations), but MLPA is not able to detect even high levels of mosaicism.

Discussion:< We have further delineated the chances of mosaicism in NF2 and resultant risks of mutation transmission to offspring in a number of different clinical situations. We also report for the first time the use of MLPA in our large NF2 series.