Genetics
TSC is a genetic disorder with an autosomal dominant pattern of inheritance, variable expressivity, and incomplete penetrance. Two-thirds of TSC cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in roughly 20% of individuals diagnosed with the disease. So far, it has been mapped to two genetic loci, TSC1 and TSC2.TSC1 encodes for the protein hamartin, is located on chromosome 9 q34, and was discovered in 1997. TSC2 encodes for the protein tuberin, is located on chromosome 16 p13.3, and was discovered in 1993. TSC2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with TSC who also develop polycystic kidney disease in childhood. TSC2 has been associated with a more severe form of TSC. However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of TSC caused by TSC2 range from 55% to 90%.TSC1 and TSC2 are both tumor suppressor genes that function according to Knudsons "two hit" hypothesis. That is, a second random mutation must occur before a tumor can develop. This explains why, despite its high penetrance, TSC has wide expressivity. Pathophysiology
Hamartin and tuberin function as a complex which is involved in the control of cell growth and cell division.
They are generally more common on toes than on fingers, develop at 15–29 years, and are more common in women than in men. Fibrous cephalic plaques are present in about 25% of people with TSC. These are raised, discoloured areas usually found on the forehead, but sometimes on the face or elsewhere on the scalp. Shagreen patches are present in about half of people with TSC, appearing in childhood. They are areas of thick leathery skin that are dimpled like an orange peel, and pigmented, they are usually found on the lower back or nape of the neck, or scattered across the trunk or thighs. The frequency of these lesions rises with age. Dental enamel pits are found in almost all adults with TSC. Intraoral fibromas are small surface-tumours found in the gums, inside the cheeks or tongue. Gum (gingival) fibromas are found in about 20-50% of people with TSC, more commonly in adults. Eyes
Retinal lesions, called astrocytic hamartomas (or "phakomas"), which appear as a greyish or yellowish-white lesion in the back of the globe on the ophthalmic examination. Astrocytic hamartomas can calcify, and they are in the differential diagnosis of a calcified globe mass on a CT scan.Nonretinal lesions associated with TSC include:

Coloboma
Angiofibromas of the eyelids
Papilledema (related to hydrocephalus)

Pancreas
Pancreatic neuroendocrine tumours have been described in rare cases of TSC. Variability
Individuals with TSC may experience none or all of the clinical signs discussed above. The following table shows the prevalence of some of the clinical signs in individuals diagnosed with TSC.