Intracranial venous malformation masquerading as a meningioma in PI3KCA-related overgrowth spectrum disorder

Am J Med Genet A. 2022 Mar;188(3):907-910. doi: 10.1002/ajmg.a.62570. Epub 2021 Dec 2.


Gain of function PIK3CA pathogenic variants have been identified in overgrowth syndromes collectively termed "PIK3CA-related overgrowth spectrum" (PROS). There are no previously reported cases of cerebrovascular venous malformations in PROS syndromes, though somatic activating PIK3CA variants have been identified in extracranial venous malformation. This study was approved by the Institutional Review Boar at Boston Children's Hospital. A 14-year-old female mosaic for the de novo p.R108H pathogenic variant in the PIK3CA gene was found to have a large tumor involving the superior sagittal sinus with mass effect on the motor cortex most consistent with a parafalcine meningioma. She underwent surgical resection with pathology demonstrating a venous malformation. PIK3CA pathogenic variants have been identified in nonsyndromic extracranial venous and lymphatic malformations as well in brain tumors, including glioma and meningioma. However, PIK3CA variants have not previously been identified in purely intracranial venous malformations. This distinction is relevant to treatment decisions, given that mTOR inhibitors may provide an alternative option for noninvasive therapy in cases of suspected venous malformation.

Keywords: PIK3CA; PROS; venous malformation.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Animals
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Female
  • Humans
  • Meningeal Neoplasms* / diagnosis
  • Meningeal Neoplasms* / genetics
  • Meningioma* / diagnosis
  • Meningioma* / genetics
  • Mutation
  • Syndrome
  • Transcription Factors / genetics
  • Vascular Malformations* / diagnosis
  • Vascular Malformations* / genetics


  • PI3KCA protein, human
  • Transcription Factors
  • Class I Phosphatidylinositol 3-Kinases