The complex appears to interact with RHEB GTPase, thus sequestering it from activating mTOR signalling, part of the growth factor (insulin) signalling pathway. Thus, mutations at the TSC1 and TSC2 loci result in a loss of control of cell growth and cell division, and therefore a predisposition to forming tumors. TSC affects tissues from different germ layers. Cutaneous and visceral lesions may occur, including angiofibroma, cardiac rhabdomyomas, and renal angiomyolipomas. The central nervous system  lesions seen in this disorder include hamartomas of the cortex, hamartomas of the ventricular walls, and subependymal giant cell tumors, which typically develop in the vicinity of the foramina of Monro.Molecular genetic studies have defined at least two loci for TSC. In TSC1, the abnormality is localized on chromosome 9q34, but the nature of the gene protein, called hamartin, remains unclear. No missense mutations occur in TSC1. In TSC2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a guanosine triphosphatase–activating protein. The specific function of this protein is unknown. In TSC2, all types of mutations have been reported; new mutations occur frequently. Few differences have yet been observed in the clinical phenotypes of patients with mutation of one gene or the other.Cells from individuals with pathogenic mutations in the TSC2 gene display abnormal accumulation of glycogen that is associated with depletion of lysosomes and autophagic impairment.
Many studies have examined whether early onset, type and severity of epilepsy associates with intellectual ability. Academic issues occur even in people with TSC who have normal intellectual ability. These are often specific learning disorders such as dyscalculia (understanding mathematics), but also include other aspects affecting school life such as anxiety, lack of social skills or low self-esteem.About half of people with TSC, when assessed for neuropsychological skills, are in the bottom 5th percentile in some areas, which indicates a severe impairment. These include problems with attention (for example, being able to concentrate on two separate things like looking and listening), memory (particularly recall, verbal and spatial working memory) and executive function (for example, planning, self-monitoring, cognitive flexibility).The psychosocial impacts of TSC include low self-esteem and self-efficacy in the individual, and a burden on the family coping with a complex and unpredictable disorder. Kidneys
Between 60 and 80% of TSC patients have benign tumors (once thought hamartomatous, but now considered true neoplasms) of the kidneys called angiomyolipomas frequently causing hematuria. These tumors are composed of vascular (angio–), smooth muscle (–myo–), and fat (–lip-) tissue. Although benign, an angiomyolipoma larger than 4 cm is at risk for a potentially catastrophic hemorrhage either spontaneously or with minimal trauma. Angiomyolipomas are found in about one in 300 people without TSC. However, those are usually solitary, whereas in TSC they are commonly multiple and bilateral.About 20-30% of people with TSC have renal cysts, causing few problems.