, Volume 13, Issue 1, pp 1–7 | Cite as

Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri

  • Pepijn van den Munckhof
  • Imke Christiaans
  • Susan B. Kenter
  • Frank Baas
  • Theo J. M. Hulsebos


Schwannomatosis is a rare hereditary cancer syndrome in which patients develop multiple non-vestibular schwannomas. The chromatin remodelling gene SMARCB1 (also known as INI1, hSNF5, and BAF47) has been identified as a schwannomatosis predisposing gene, being involved in a subset of sporadic and familial cases. Recent studies have shown that SMARCB1 may also be involved in the development of multiple meningiomas. Previously, we demonstrated that the SMARCB1 exon 2 missense mutation c.143 C > T segregates with the presence of meningiomas in five members of a large family with multiple meningiomas and schwannomas. We extended our genetic analyses by screening 44 additional at-risk family members and identified 13 new carriers. Eleven of these were subjected to magnetic resonance imaging (MRI) of brain and spine. In addition, we analyzed four meningiomas and two schwannomas from family members for the presence of schwannomatosis-specific changes. We found in each tumor retention of the SMARCB1 exon 2 mutation, acquisition of an independent neurofibromatosis type 2 (NF2) gene mutation, and loss of heterozygosity at SMARCB1 and NF2 by loss of the wild-type copy of both genes. The MRI scans revealed one or more falx meningiomas in seven of 11 (64%) newly identified SMARCB1 mutation carriers. We conclude that the SMARCB1 exon 2 missense mutation in this family predisposes to the development of meningiomas as well as schwannomas, occurring via the same genetic pathways, and that this mutation preferentially induces cranial meningiomas located at the falx cerebri.


Schwannomatosis Multiple meningiomas SMARCB1 mutation Falx meningioma 



The authors thank the family members for their participation in this study. We are indebted to Prof Dr. D. Troost (Neuropathology Department, Academic Medical Center, Amsterdam), Dr M.G. Havenith (Pathology Department, Isala Clinics, Zwolle), and D. Stomphorst (Pathology Department, Leiden University Medical Center, Leiden) for providing tumor materials.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Pepijn van den Munckhof
    • 1
  • Imke Christiaans
    • 2
  • Susan B. Kenter
    • 3
  • Frank Baas
    • 3
  • Theo J. M. Hulsebos
    • 3
  1. 1.Department of NeurosurgeryAcademic Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Clinical GeneticsAcademic Medical CenterAmsterdamThe Netherlands
  3. 3.Department of Genome AnalysisAcademic Medical CenterAmsterdamThe Netherlands

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