Everolimus for cognition/autism in children with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) has been recognized as an important clinical entity for well over 150 years. The recent pace of discovery has been thrilling, with gene identification ( TSC1 and TSC2 ), insights into cellular signaling (dysregulation of mTOR kinase), and the subsequent rational application of the mTOR inhibitors sirolimus and everolimus to treat various aspects of TSC. These advances culminated in Food and Drug Administration (FDA) approval of everolimus for TSC-associated subependymal giant cell astrocytomas in 2010,1 the angiomyolipomas in 2012, and complex partial seizures in 2018.2 Sirolimus is effective for seizures in TSC3 and is FDA-approved for the treatment of lymphangioleiomyomatosis, a progressive lung disease largely seen in adult women with TSC. Both agents have shown efficacy for cutaneous hamartomas and cardiac rhabdomyomas.