History and clinical epidemiology of NF2-related schwannomatosis

NF2-related schwanomatosis (NF2-SWN) (previously Neurofibromatosis 2) as characterised by bilateral vestibular schwannomas (VS) was first described in 1822. However, due to the erroneous conflation of individuals with bilateral eighth nerve tumours with von Recklinghausen disease (currently Neurofibromatosis 1, NF1) in 1917 the literature was confusing for much of the 20th century. Even when the conditions were separated officially in 1987 (with separate localisation of the genes), NF2-SWN remained classified as a neurofibromatosis despite the tumours pathognomonic for NF1, neurofibromas, not being a feature of NF2-schwannomatosis. It is only in 2022 that NF2-SWN was correctly delineated as a schwannomatosis. The epidemiology of NF2-SWN has only been possible to delineate after the separation of NF2-SWN from the much more frequent nerve sheath predisposing tumour condition NF1. Two research groups have published on the birth prevalence and population prevalence of NF2-SWN in the UK and Finland. The most highly ascertained assessment of NF2-SWN cases from the Manchester region of England (population 4.8 million) gave a diagnostic prevalence of 1 in 50,500 and calculated birth prevalences of 1 in 27,956 respectively. However, an updated prevalence across England in 2024 (population 55 million) gave a prevalence of at least 1 in 58,000. NF2-SWN usually presents with bilateral vestibular schwannoma, but can present with meningioma or spinal tumour or ophthalmic features before a VS diagnosis or with a unilateral VS and other tumours and rarely with a unilateral VS alone. Molecular testing is now extremely helpful in confirming the diagnosis of mosaic (present in up to 50% of de novo cases) versus germline NF2 and distinguishing from other tumour predisposition conditions especially in childhood or cases with less common presentation. This chapter summarises the clinical epidemiology of NF2-SWN differentiating the condition from the overlapping non NF2-SWN.