Such variants are often overactivating variants of the phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin pathway (PI3K/AKT/mTOR) (pathogenic variants in PIK3CA in PROS, KTS; mutations of AKT1 in PS, of AKT2 in hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH), of mTOR in Smith-Kingsmore syndrome (SKS)) or deactivating variants in repressors of this pathway (the phosphatase and tensin homolog (PTEN) in PHTS and PS) (Yehia et al., 1993). This evidence concerns the gene PTEN and PTEN hamartoma tumor syndrome.