PT - JOURNAL ARTICLE AU - Forde, Claire AU - Smith, Miriam J AU - Burghel, George J AU - Bowers, Naomi AU - Roberts, Nicola AU - Lavin, Tim AU - Halliday, Jane AU - King, Andrew Thomas AU - Rutherford, Scott AU - Pathmanaban, Omar N AU - Lloyd, Simon AU - Freeman, Simon AU - Halliday, Dorothy AU - Parry, Allyson AU - Axon, Patrick AU - Buttimore, Juliette AU - Afridi, Shazia AU - Obholzer, Rupert AU - Laitt, Roger AU - Thomas, Owen AU - Stivaros, Stavros Michael AU - Vassallo, Grace AU - Evans, D Gareth TI - <em>NF2</em>-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study AID - 10.1136/jmg-2024-110065 DP - 2024 Jun 26 TA - Journal of Medical Genetics PG - jmg-2024-110065 4099 - http://jmg.bmj.com/content/early/2024/06/25/jmg-2024-110065.short 4100 - http://jmg.bmj.com/content/early/2024/06/25/jmg-2024-110065.full AB - Objectives New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed.Methods The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England’s specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed.Results 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p&lt;0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1-related schwannomatosis and SMARCB1-related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4–18.4 times lower than NF2.Conclusions This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling.Data are available upon reasonable request. Anonymised data can be requested.