Tuberous Sclerosis

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by a pathogenic variant in TSC1 or TSC2. These genes normally produce hamartin and tuberin, which restrain the mechanistic target of rapamycin complex 1 (mTORC1). When that brake is lost, mTORC1 remains abnormally active, promoting cell growth and the formation of hamartomas in multiple organs. The lesions are usually benign in the sense that they are not metastatic cancers, but their location can make them dangerous. A cortical tuber can disrupt neural circuits and produce seizures. A subependymal giant cell astrocytoma (SEGA) can enlarge near the foramen of Monro and obstruct cerebrospinal-fluid flow. A renal angiomyolipoma can bleed because it contains abnormal blood vessels. A cardiac rhabdomyoma can interfere with cardiac output in an infant even though it may later regress. The clinical pattern is therefore multisystem rather than purely neurological. Common clues include hypomelanotic macules, seizures or infantile spasms, cortical dysplasias, subependymal nodules, SEGAs, renal angiomyolipomas, cardiac rhabdomyomas, retinal hamartomas, and neurodevelopmental or behavioural differences. Pulmonary lymphangioleiomyomatosis (LAM), particularly in adult women, can cause progressive breathlessness or spontaneous pneumothorax....