Tuberous sclerosis complex

Tuberous sclerosis complex is a complex systemic disorder characterized by tumorigenic changes in numerous organs. Mainly affected are the brain, skin, eyes, heart, lungs, and kidneys. Characteristic of the disease are facial angiofibromas, Koenen tumors (sub- and periungual fibroids), fibral plaques on the scalp and forehead, renal angiomyolipomas, subependymal knots or multiple cortical tubers and hamartomas of the retina.

In children, the symptoms can be very discrete. Most patients have epilepsy, mostly generalized and difficult to control.

Neuropsychiatric symptoms such as mental retardation, attention deficit/hyperactivity disorder, autism spectrum disorders, self-injurious behavior, anxiety and obsessive-compulsive disorder have also been reported. Lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, and pulmonary cysts may develop in adulthood and manifest with dyspnoea, pneumothorax or chylothorax. The main complications involve the central nervous system (seizure, increased intracranial pressure), the kidneys (rupture of cysts and angiomyolipomas) and in adults the lungs (rupture of alveoli in lymphangioleiomyomatosis). The disease is inherited autosomal dominant. It is based on mutations of the genes TSC1 (tuberous sclerosis gene 1, gene locus 9q34) and TSC2 (tuberous sclerosis gene 2, gene locus 16p13.3), which result in disruptions of the proteins hamartin (TSC1) and tuberin (TSC2). These form a protein complex which acts mitosis-inhibiting and thus indirectly as a tumor suppressor. The consequence of the mutations is an unrestrained cell growth, which explains the mostly benign tumors. Part of the signal chain is the rapamycin complex 1 (mTORC1).