Chapter 30 - Tuberous Sclerosis

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas and hamartias in several organ systems.TSC is a relatively variable clinical syndrome, in which several pathologic manifestations are highly specific for the disease. The cardinal feature is the cortical tuber, which is a distinctive form of brain hamartia. Hamartias and hamartomas usually involve several different organ systems in TSC patients, in addition to the brain. Cortical tubers, the hallmark finding in TSC, are found grossly as firm, smooth, somewhat raised, pale lesions of the cerebral cortex. Subependymal giant cell astrocytomas (SEGAs) develop in 5-10% of TSC patients. These lesions represent a form of subependymal nodule (SEN) with progressive growth and enlargement to a size ›1 cm. Mental retardation and developmental disabilities are major issues for many TSC patients. About half of TSC patients have normal intelligence, while the other half have mental disability ranging from mild to profound. Angiomyolipomas (AMLs) are the most common TSC kidney lesion, seen in about 75% of children by adolesence using ultrasound imaging. AMLs often occur as multiple lesions in both kidneys, which can grow to become nearly confluent, making it difficult to distinguish by imaging studies between normal renal parenchyma and AML. Cutaneous findings are present in over 80% of TSC patients, and are the most easily recognized sign of the disease. Most lesions are of minor significance, but facial angiofibromas can be a significant cosmetic issue. Cardiac rhabdomyomas are common in TSC infants and children. These lesions can be up to several centimeters in diameter and consist of glycogenfilledmyocytes.