NF2-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study.
J Med Genet
; 61(9): 856-860, 2024 Aug 29.
Article
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| MEDLINE
| ID: mdl-38925914
ABSTRACT
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<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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Cutáneas
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Neurofibromatosis 2
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Neurofibromatosis
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Neurofibromina 2
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Proteína SMARCB1
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Neurilemoma
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Med Genet
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J. med. genet. (Online)
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Journal of medical genetics (Online)
Año:
2024
Tipo del documento:
Article