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Objectives: Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2., Methods: Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2 , LZTR1 and SMARCB1 on blood and tumour DNA samples when available., Results: Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1 -associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%-2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004)., Conclusions: Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Onset of symptoms in severe sporadic neurofibromatosis type 2 (NF2) is typically within childhood; however, there is poor awareness of presenting features in young children, potentially resulting in delayed diagnosis and poorer outcome. We have reviewed presentation of sporadic paediatric NF2 to raise awareness of early features, highlighting those requiring further investigation., Design: Patients diagnosed with NF2 at age ≤16 and seen between 2012 and 2015 were notified via the British Paediatric Neurology Surveillance Unit or identified through the English NF2 service., Results: Epidemiological data estimate that 1 in 110 611 births are affected with childhood-onset NF2. Notes of 32 patients with sporadic NF2 were reviewed. Of those presenting under the age of 5, 89% (17/19) had ocular, 74% (14/19) dermatological and 58% (11/19) neurological signs; in 84% (16/19) features were multisystemic. Sixty-six per cent (21/32) had ≥1 atypical feature, including cerebellar hypoplasia in three cases (9%) and focal cortical dysplasia in five out of seven seizure-related presentations. Five cases presented with a sometimes transient or intermittent cranial nerve mononeuropathy. The mean delay to diagnosis was 3.16 years; in eight cases (25%) this exceeded 6 years. Most significant delay occurred in mononeuropathy, ophthalmological and/or seizure presentations, with a mean delay of 3, 4.5 and 6 years, respectively. Eighty-four per cent (27/32) of cases needed intervention in childhood., Conclusions: All non-vestibular schwannoma NF2 presentations in childhood had significant diagnostic delay. We emphasise the importance of detailed assessment of skin and eyes in unusual presentations and propose an aide to prompt timely referral to specialist services., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: It is widely accepted that stereotactic radiosurgery (SRS) is less effective in controlling NF2-related vestibular schwannomas (VS-NF2), than sporadic VS. Concerns persist regarding the risks of malignant transformation and the development of secondary tumours. In recent years there has been an increase in the number of centres offering SRS and fractionated stereotactic radiotherapy (SRT) services for VS. The NF2 National Commissioning Group service framework has recommended limiting radiation therapies for VS-NF2 to SRS (Gamma Knife) provided in Sheffield. The aims of this review were to: 1) Establish the current provision of SRT and SRS services in England. 2) Determine the radiation therapies employed for NF2 patients since 2000. 3) Determine the feasibility of identifying a national cohort of NF2 patients in England who have received radiation therapy since 2000., Methods: The lead clinicians managing VS patients in the major regional neurosurgical units in England, and those providing SRS services to NF2 patients were contacted and when possible, databases were examined., Results: A total of 18 NHS centres and 2 private centres were included. This included the four NF2 'hub centres' (Cambridge, London, Oxford and Manchester). Their NF2 databases identified 4, 8, 23 and 42 VS-NF2 treatments with SRS or SRT, respectively since 2000. Eleven centres reported that they had referred VS-NF2 patients exclusively to Sheffield. Each estimated that they had referred no more than one patient per year. The survey identified four Gamma Knife Centres and six Linac SRS/SRT centres with the capacity to treat VS and VS-NF2 patients. Of these, four centres confirmed that they had treated VS-NF2 patients., Conclusion: Since 2000 fewer than 100 SRS and SRT treatments have been undertaken for VS-NF2 patients. Approximately 60% of these have been performed in Sheffield. There is considerable uncertainty regarding the role of radiation therapy in the management of VS-NF2 and consequently a range of views and practice.

Objective: To determine the incidence of vestibular schwannoma (VS) in sporadic, neurofibromatosis type 2 (NF2) germ-line and mosaic form in a 10-year period., Study Design: Review of all incident cases of VS presenting to the four main neurosurgical centers for a population of 4.1 million from 1990 to 1999 and cross-referencing with the regional cancer registry., Setting: Population based., Patients: All patients presenting with VS detected on magnetic resonance imaging scan., Results: A total of 419 sporadic and 64 NF2-related VS were identified over the study period. This represented an incidence of 10.4 per million per year for sporadic VS and 11.8 per million per year including NF2-related tumors. The incidence rose to 14 per million per year in the latter 5 years. The NF2 patient diagnoses represent an estimated birth incidence of 1 in 25,000, and 7% of the patients with VS had NF2, which is higher than previous estimates., Conclusions: The incidence of VS is rising almost certainly due to increasing diagnosis in the magnetic resonance imaging era. At current rates, 1 per 1,000 individuals will be diagnosed with VS in their lifetime. More VS than previously thought are due to NF2, which may be because of recognition of mosaic forms of the disease.

The results of a U.K. study of 145 cases of type 2 neurofibromatosis has shown generally very poor operative results in terms of hearing and facial nerve preservation. Only 9 out of 118 vestibular schwannoma (acoustic neuroma) operations resulted in any clinically detectable hearing preservation and only 32 left the patient with good or normal (House grade I or II) ipsilateral facial nerve function. Although operation is still the definitive treatment of vestibular schwannoma (acoustic neuroma) and may be a lifesaving procedure, it appears that the evidence in favour of early operation is only valid when carried out in highly specialized centres. The special problems of NF2 cases who may go on to develop multiple spinal and cranial tumours making them wheelchair bound and blind as well as deaf warrants a careful experienced approach. Timing of operations may be critical for the enhancement of useful years of quality life. We therefore propose the setting up of a national NF2 register, with the management of cases at a few supraregional centres.