<italic>mTOR</italic> mutations in Smith‐Kingsmore syndrome: Four additional patients and a review.

Smith‐Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non‐neurological features. Germline or mosaic mutations of the <italic>mTOR</italic> gene have been detected in all patients. The <italic>mTOR</italic> gene is a key regulator of cell growth, cell proliferation, protein synthesis and synaptic plasticity, and the mTOR pathway (PI3K‐AKT‐mTOR) is highly regulated and critical for cell survival and apoptosis. Mutations in different genes in this pathway result in known rare diseases implicated in hemi/megalencephaly with epilepsy, as the tuberous sclerosis complex caused by mutations in <italic>TSC1</italic> and <italic>TSC2</italic>, or the <italic>PIK3CA</italic>‐related overgrowth spectrum (PROS). We here present 4 new cases of SKS, review all clinical and molecular aspects of this disorder, as well as some characteristics of the patients with only brain <italic>mTOR</italic> somatic mutations. [ABSTRACT FROM AUTHOR]