- Most MTOR mutations identified to date are de novo.
- Mutations can be either germline (constitutional) or post-zygotic (mosaic).
- MTOR mutations are known to be associated with Gain of Function (GOF) of PI3K-AKT-MTOR pathway activity.
- Preliminary genotype-phenotype correlations suggest that phenotypes depend on tissue distribution, levels of mosaicism and type of the MTOR mutation with three general correlations appreciated:
- The most severe GOF mutations (i.e. S2215F) are associated with severe overgrowth and cellular dysplasia causing HMEG or FCD.
- Intermediate GOF mutations are, with rare exceptions, associated with MEG and PMG
- The least severe GOF mutations are associated with diffuse MEG with apparently normal gyral pattern.
MTOR