Probability of bilateral disease in people presenting with a unilateral vestibular schwannoma

Abstract

Background-Some 4%-5% of those who develop vestibular schwannomas have neurofibromatosis type 2 (NF2). Although about 10% of these patients present initially with a unilateral vestibular schwannoma, the risk for a patient with a truly sporadic vestibular schwannoma developing contralateral disease is unknown. Methods-A United Kingdom survey of 296 patients with NF2 was reviewed for laterality of vestibular schwannoma at presentation and the presence of other NF2 related features. The time to presentation of bilateral disease was calculated for patients presenting with a unilateral tumour. Mutation analysis of the NF2 gene was carried out on all available cases presenting initially with unilateral disease. Results-Of 240 patients with NF2 with vestibular schwannomas, 45 (18%; 32 sporadic, 13 familial) had either a unilateral tumour or delay in detection between the first and contralateral tumours. Among those tested for NF2 mutations, eight of 27 and nine of 13 were identified among sporadic and familial cases respectively. Sporadic cases showed a high female to male ratio and 19 of 32 have not as yet developed a contralateral tumour (mean 4.1 years after diagnosis of the first). Thirteen of 32 sporadic patients developed a contralateral tumour (mean 6.5 years after the first tumour diagnosis, range 0-22 years) compared with 11 of 13 familial patients (mean delay 5 years, range 0-16 years). Seven of the 45 patients had neither a family history of NF2 nor evidence of related tumours at initial presentation (six before the age of 35 years). Conclusion-The risk of patients with sporadic unilateral vestibular schwannomata developing a contralateral tumour in the absence of family history or other features of NF2 is low, but those presenting with other neurogenic tumours in addition to vestibular schwannoma are at high risk of harbouring an NF2 mutation in at least a proportion of their somatic cells. (J Neurol Neurosurg Psychiatry 1999;66:764-767) Keywords: neurofibromatosis type 2; somatic mosaicism; mutation; vestibular schwannoma Type 2 neurofibromatosis (NF2) is an autosomal dominant inherited condition characterised by development of bilateral vestibular schwannomas, schwannomas of other cranial, spinal, and cutaneous nerves, and cranial and spinal meningiomas.1-3 The National Institutes of Health (NIH) defined diagnostic criteria for NF2 in 1987 4 and modified criteria to allow for sporadic cases have since been published. 2According to NIH criteria (table 1) a person with bilateral vestibular schwannomas is assumed to have NF2 and 50% of oVspring would be predicted to be aVected. As the isolation of the NF2 gene in 1993 5 6 mutation studies have included reports of germ line mutations.7-9 Detection rates using routine methodology have been disappointingly low even in classically aVected patients and cannot therefore be used as a means of excluding the condition.At presentation, 10%-20% of patients with NF2 have a unilateral vestibular schwannoma, although other features of the disorder may be identi...

Cochlear nucleus auditory prostheses

“…To date, more than 500 persons have received auditory brainstem implants. However, the prevalence of NF2 is approximately 1 in 40,000 live births with a high probability of bilateral acoustic tumors (Evans et al, 1992(Evans et al, , 1999, so there are many thousands of persons who could benefit from these devices, and with little risk or discomfort in addition to those related to the surgical removal of the tumors. At present, the prospects are uncertain for improving the performance of central auditory prostheses for persons with NF2, in part because it is unclear why they perform so poorly with the existing devices.…”

Neurofibromatosis Type 2

“…8,22 Although the NIH criteria for NF2 imply that all patients with NF2 develop bilateral vestibular schwannomas, some researchers are not convinced of this. 23 Evans and colleagues 23 based their conclusion on the observation of a possible variant form of NF2 manifesting with skin and spinal tumors in the absence of vestibular schwannomas. Nonetheless, the phenotype generally is reflective of the underlying disorder.…”

Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]

“…48 -52 Splice site mutations have been associated with both mild and severe disease 49,51,53 and may be milder if occurring in the 3Ј half of the gene. 54 Missense mutations are usually mild, often causing the mildest form of NF2. 35,52 In general, truncating mutations (frameshift and nonsense) show a significantly more severe pattern of tumors and are associated with greater disease-related mortality than missense splice site and large deletions.…”