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Somatic mutations rather than viral infection classify focal cortical dysplasia type II as mTORopathy

Ingmar Blümcke1, Harvey B Sarnat

  • 1aDepartment of Neuropathology, University Hospital Erlangen, Erlangen, Germany bEpilepsy Center, Cleveland Clinic Foundation, Cleveland, Ohio, USA cDepartment of Paediatrics dDepartment of Pathology (Neuropathology) eDepartment of Clinical Neurosciences, University of Calgary Faculty of Medicine, Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.

Current Opinion in Neurology
|February 4, 2016
PubMed
Abstract

Insights

Focal cortical dysplasia type II (FCD II) is linked to somatic mutations in the mTOR pathway, not viral infections. The timing of these mutations during neurodevelopment determines lesion size.

Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Focal cortical dysplasia type II (FCD II) has proposed etiologies including somatic mutations in the mammalian target of rapamycin (mTOR) pathway and human papilloma virus (HPV) infection.
  • Available data on the role of HPV in FCD II remain controversial, necessitating a review of the evidence.

Purpose of the Study:

  • To review and discuss the contradicting etiologies of FCD II, focusing on the roles of somatic mutations and viral infections.
  • To clarify the classification of FCD II within the spectrum of mTORopathies based on genetic and histopathological findings.

Main Methods:

  • Review of genetic studies in FCD II.
  • Analysis of data linking mTOR pathway activation to FCD II.
  • Evaluation of evidence for viral infection in FCD II.
  • Discussion of neuroembryologic principles of cortical development.

Main Results:

  • Genetic studies strongly support somatic mutations in mTOR pathway genes as a cause of FCD II.
  • The timing of somatic mutations during neuroblast proliferation correlates with the size and extent of FCD II lesions.
  • Recent data do not support viral infection as an etiology for FCD II.
  • FCD II is classified as an mTOR-related disorder (mTORopathy) based on genetic and histopathological evidence.

Conclusions:

  • FCD II is primarily an mTOR-related disorder (mTORopathy) driven by somatic mutations.
  • The developmental timing of these mutations explains the varying lesion characteristics in FCD II.
  • Viral etiologies are not supported by current evidence for FCD II.

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