What are the implications in individuals with unilateral vestibular schwannoma and other neurogenic tumors?
OBJECTIVE
Individuals who develop a unilateral vestibular schwannoma (VS) and other neurogenic tumors are at high risk of having the inherited condition neurofibromatosis Type 2 (NF2). The risk of bilateral disease and transmission risk to offspring are important in surgical planning and counseling. The authors have attempted to resolve these risks.


METHODS
A large NF2 dataset was interrogated for individuals who had initially presented with a unilateral VS and other tumors before developing bilateral disease, to assess the contralateral and offspring risks.


RESULTS
Ninety-six patients with a unilateral VS and additional neurogenic tumors had a bilaterality rate of 48% at 20 years in those initially diagnosed when > 18 years of age and 82% if presenting earlier. Constitutional NF2 mutations were found in blood in 25 (27%) of 92, but 13 (76%) of 17 patients presenting with unilateral VS at < or = 18 years of age. Tumor analysis suggests that the vast majority of the remainder are mosaic for an NF2 mutation.


CONCLUSIONS
Patients with unilateral VS and other NF2-related tumors who fulfill Manchester criteria have a high risk of developing a contralateral tumor, especially if presenting in childhood. Transmission risks are reduced for offspring, particularly in the older patients who are likely to be mosaic.
Evans
D Gareth R
DG
Academic Unit of Medical Genetics, Regional Genetics Service and National Genetics Reference Laboratory, St. Mary's Hospital, Manchester, United Kingdom. Gareth.evans@cmmc.nhs.uk
Ramsden
Richard T
RT
Shenton
Andrew
A
Gokhale
Carolyn
C
Bowers
Naomi
N
Huson
Susan M
SM
Wallace
Andrew J
AJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D016208:Databases, Factual; D005260:Female; D016515:Genes, Neurofibromatosis 2 / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009464:Neuroma, Acoustic / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree