In tuberous sclerosis, the protein products of the TSC1 and TSC2 genes, hamartin and tuberin, act together in regulating the P13 kinase-Akt-mTOR-S6 kinase cell growth pathway. This finding raises the possibility that drugs could substitute for the role of the hamartin-tuberin complex in this pathway and thereby ameliorate some aspects of the disease in affected individuals. One such drug, rapamycin, is currently beginning evaluation.
Mutations are still only found in two thirds of affected individuals and a negative mutation screen should not be taken as evidence of absence of the disease. The need for detailed clinical examination and investigation remains paramount, especially in evaluating parents.
Seizures in the first 5 years of life, but particularly in the first year, including infantile spasms, require urgent intervention. We do not advocate screening but we do suggest urgent evaluation for possible raised intracranial pressure secondary to giant cell astrocytomas and for bleeding from renal angiomyolipomas where preserving renal function is a priority.