Tuberous sclerosis complex: advances in diagnosis, genetics, and management

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem neurocutaneous syndrome characterized by the development of multiple hamartomas distributed throughout the body, skin, brain, heart, kidneys, liver, and lungs. Two-thirds of patients represent sporadic mutations. The classic triad is seizures, mental retardation, and cutaneous angiofibromas. However, the full triad occurs in only 29% of patients; 6% of them lack all three of them. Two tumor suppressor genes responsible for TSC have been identified: TSC1 gene on chromosome 9 and TSC2 on chromosome 16. This article highlights the most recent significant advances in the diagnosis and genetics of TSC, along with a discussion on the limitations and the usefulness of the revised 1998 clinical criteria for the tuberous sclerosis complex. The "ash leaf" macule often comes in other shapes, such as round; most are polygonal, usually 0.5 cm to 2.0 cm in diameter, resembling a thumbprint. Since the death of its describer, Thomas Fitzpatrick, we call each a "Fitzpatrick patch." Special attention is paid in this work to TSC treatment options, including therapeutic trials with rapamycin, also known as sirolimus.

After completing this learning activity, participants should familiar with tuberous sclerosis complex, its cutaneous signs and systemic findings stratified by patient age, its genetics, and the potential for meaningful therapeutic intervention.