Molecular characteristics

  • Most PIK3CA mutations identified to date are activating mutations of the PI3K-AKT-MTOR pathway.
  • Most identified PIK3CA mutations are postzygotic (or mosaic; i.e. present in a small fraction of cells).

Preliminary genotype-phenotype correlations suggest that phenotypes depend on tissue distribution, levels of mosaicism and type of PIK3CA mutation with three general correlations identified:

  • The most severely activating mutations are associated with severe overgrowth and cellular dysplasia causing epilepsy, CLOVES, or severe focal phenotypes (e.g. vascular or lymphatic malformations).
  • Intermediately activating mutations are, with rare exceptions, associated with MEG and PMG (i.e. MCAP syndrome), and rarely other phenotypes (e.g. vascular or lymphatic malformations).
  • The least severe mutations are associated with diffuse brain overgrowth with apparently normal gyral pattern.