Tuberous Sclerosis: Skin Findings and Systemic Monitoring

Overview / Definition Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in either the TSC1 or TSC2 genes, leading to the formation of non-malignant tumors, known as hamartomas, in multiple organs. It is a multisystem disorder that predominantly affects the skin, brain, kidneys, heart, and lungs. Epidemiology Tuberous sclerosis complex has an estimated prevalence of approximately 1 in 6,000 live births. It affects both genders equally and occurs worldwide, with no known ethnic predisposition. The condition can arise due to autosomal dominant inheritance patterns, but two-thirds of cases are due to new mutations. Pathophysiology / Mechanism The underlying mechanism of TSC involves abnormalities in the mTOR (mammalian target of rapamycin) signaling pathway, which regulates cell growth and proliferation. Mutations in the TSC1 gene (located on chromosome 9) produce the protein hamartin, while mutations in the TSC2 gene (on chromosome 16) produce tuberin. Loss of function of these proteins leads to uncontrolled cell growth, resulting in the characteristic tumors and skin lesions. Clinical Presentation The skin findings associated with tuberous sclerosis are diverse and can be classified into several categories: Adenoma sebaceum: Also known as angiofibromas, these are reddish-brown papules typically found on the face, particularly over the nose and cheeks. Shagreen patches: These are raised, thickened patches of skin with a rough texture, often located on the lower back. Hypomelanotic macules: These are flat, white spots that can occur anywhere on the body, commonly seen in clusters. Facial angiofibromas: These lesions are typically present in childhood and become more prominent with age. Periungual fibromas: Fibromas that develop around the nails, often seen in adults. Additional findings may include café-au-lait spots, fibrous plaques (especially in the axillary region), and lamellar ichthyosis. Diagnosis / Workup The diagnosis of tuberous sclero