- 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.