Schwannomatosis: a genetic and epidemiological study

<jats:sec><jats:title>Objectives</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>NF2</jats:italic>, <jats:italic>LZTR1</jats:italic> and <jats:italic>SMARCB1</jats:italic> on blood and tumour DNA samples when available.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>NF2</jats:italic> causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. <jats:italic>LZTR1</jats:italic>-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).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.</jats:p></jats:sec>