Dynamic tubers in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) has a rich history and special place in Neurology given its myriad and multiorgan manifestations that have intrigued physicians for more than 100 years.1 Within the brain, the eponymic “tubers” and subependymal giant cell astrocytomas are the main clinically relevant manifestations. These are usually monitored using brain MRI every 1 to 3 years in patients younger than 25 years.2 Tubers, in particular, have been the focus of extensive study based on the generally accepted view that they are the main contributors to epilepsy as well as to autism, intellectual disabilities, and behavioral problems in patients with TSC. This view of tubers now appears to be relatively simplistic given greatly increased knowledge over the past decade about the normal function of the causative TSC1 (encodes hamartin) and TSC2 (encodes tuberin) genes, and their downstream signaling pathways, most notably the mammalian target of rapamycin (mTOR) kinase.3