SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome

Eur J Med Genet. 2023 Jul;66(7):104784. doi: 10.1016/j.ejmg.2023.104784. Epub 2023 May 8.

Abstract

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant. Family segregation study detected the SMARCE1 variant in the asymptomatic father and in the asymptomatic sister who, nevertheless, presents 2 spinal lesions. Germline heterozygous loss-of-function (LoF) variants in SMARCE1, encoding a protein of the chromatin-remodeling complex SWI/SNF, have been described in few familial cases of susceptibility to meningioma, in particular the CCM subtype. Our case confirms the role of NGS in investigating predisposing genes for meningiomas (multiple or recurrent), with specific regard to SMARCE1 in case of pediatric CCM. In addition to the age of onset, the presence of familial clustering or the coexistence of multiple synchronous meningiomas also supports the role of a genetic predisposition that deserves a molecular assessment. Additionally, given the incomplete penetrance, it is of great importance to follow a specific screening or follow-up program for symptomatic and asymptomatic carriers of pathogenic variants in SMARCE1.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Chromosomal Proteins, Non-Histone / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Germ-Line Mutation
  • Humans
  • Loss of Heterozygosity
  • Meningeal Neoplasms* / diagnosis
  • Meningeal Neoplasms* / genetics
  • Meningeal Neoplasms* / pathology
  • Meningioma* / diagnosis
  • Meningioma* / genetics
  • Meningioma* / pathology
  • Transcription Factors / genetics

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCE1 protein, human
  • Transcription Factors