The tuberous sclerosis complex: a comprehensive review

Tuberous sclerosis was first reported by von Recklinghausen in 1862 and named by Bourneville in 1880. Transmission is autosomal dominant, but roughly 65% to 85% of the patients arise via spontaneous mutation. The incidence of tuberous sclerosis is estimated between 1:6,000 and 1:10,000 individuals. The notion of the “classic triad” of epilepsy, mental retardation, and facial angiofibromata (adenoma sebaceum) has been frequently cited in literature. However, few affected individuals develop all of the aforementioned signs, and emphasis of these limited features is misleading. It seems more appropriate to recognize that tuberous sclerosis complex may present as a wide spectrum of disease. The diagnostic criteria for Tuberous Sclerosis Complex were revised by a subcommittee at the recent Tuberous Sclerosis Consensus Conference. These clinical diagnostic criteria are outlined in Table 1. Pathologically, tuberous sclerosis is a disorder of cellular migration, proliferation, and differentiation. Manifestations may be systemic and variable. A variety of associated lesions have been reported in the literature including subependymal brain nodules and calcifications, astrocytomas, retinal phacomas, sclerotic bone lesions, dental enamel pitting, and hamartomatous or cystic lesions of the brain, heart, lungs, kidneys, spleen, liver, uterus, and soft tissues. Although many of the clinical manifestations of tuberous sclerosis are secondary to hamartomatous growths, true neoplasms do occur, particularly in the kidneys and brain. Depending on the degree of clinical expression and organ involvement specifically, select patients may experience significant morbidity and mortality. Advances in genetics, imaging modalities, medical therapies, and surgical techniques have unmasked some of the mysteries surrounding this fascinating disorder and, undoubtedly, will continue to affect the associated complications.