Tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of hamartomas in multiple organs. It is caused by mutations in either the TSC1 gene on chromosome 9 or the TSC2 gene on chromosome 16. Both genes are tumour suppressor genes and the protein products of the two genes, hamartin and tuberin, co-localize in the cell and help regulate cell growth by inhibiting the mammalian target of rapamycin (mTOR) in the akt-mTOR-S6 kinase cell growth pathway. The discovery of the TSC proteins’ role in this intracellular pathway has recently lead to investigation of chemotherapeutic agents, such as rapamycin (sirolimus), that also influence this pathway and that may partly substitute for their role in regulating cell growth. Clinically, the disease commonly causes epilepsy, learning difficulties and behavioural problems (autism, hyperactivity and sleep disturbance), although as many as half of affected individuals may have a normal IQ. Life-threatening hamartomas may develop during life in the kidneys (renal angiomyolipomas) and brain (subependymal giant cell astrocytomas). Clinicians need to watch carefully for these complications. Patients with TSC will require multidisciplinary clinical involvement and, preferably, this should be coordinated through a specialist TSC clinic.