Somatic mosaicism in neurofibromatosis 2: Prevalence and risk of disease transmission to offspring

Neurofibromatosis 2 (NF2), an autosomal dominant disorder that is characterised by tumours of cells of neural crest origin, is caused by inactivating mutations of the NF2 gene on chromosome 22q12.1,2 Bilateral vestibular schwannomas are the most frequent manifestation of the disease, but other central and peripheral nervous system schwannomas, cerebral meningiomas, and ocular abnormalities are also common.3–5 The birth incidence of NF2 is 1 in 33 000 to 1 in 40 000.6 Constitutional NF2 mutations have been found in 30-60% of NF2 patients, and genotype-phenotype correlations have been substantiated.7–12

Half of NF2 patients are new mutations,6 in whom constitutional NF2 mutations can occur either in parental germline cells (prezygotic) or in cells after fertilisation (postzygotic). Postzygotic mutations can result in mosaicism, defined as the presence of a mutation, deletion, or chromosomal abnormality in a group or population of cells.13 Owing to the rarity of NF2, most previous reports of mosaicism in NF2 have been limited in scope,14–16 although a recent study estimated that 25% of NF2 patients with new mutations are mosaic.17 In this study, we describe mutational analysis of 27 mosaic cases of NF2 and the results of genetic testing in their children.