| Source: |
Forde, C, Smith, M J, Burghel, G, Bowers, N, Roberts, N, Lavin, T, Halliday, J, King, A, Rutherford, S A, Pathmanaban, O, Lloyd, S, Freeman, S, Halliday, D, Parry, A, Axon, P, Buttimore, J, Afridi, S, Obholzer, R, Laitt, R, Thomas, O, Stivaros, S, Vassallo, G & Evans, D G 2024, 'NF2-related Schwannomatosis and other schwannomatosis : an updated genetic and epidemiological study', Journal of Medical Genetics, vol. 61, no. 9, pp. 856-860. |
| Description: |
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 amongst 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 specialized service. Diagnostic prevalence was assessed on 01/02/2023. 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 were 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 |