Tuberous sclerosis complex: Skin and heart: Pivotal common and early signs

Tuberous sclerosis (TSC) is a genetic neurocutaneous disease resulting from mutation in TSC1 or TSC2 gene and associated with development of multiple tumors in different organs including skin, brain, heart, and kidney. TSC is associated with high incidence of epilepsy (70-90%) and associated with seizures cognitive impairment (50-60%). Skin and cardiac manifestations are the earliest detectable signs of TSC, facilitating diagnosis and intervention before seizures. Skin manifestations are common and include hypomelanotic macules, facial angiofibromas, fibrous cephalic plaques, shagreen patches and periungual fibromas. Most cutaneous findings do not result in severe clinical consequences, however, they may cause esthetical discomfort and in rare cases bleeding, irritation, and disfigurement. Current therapies include photoprotection, topical and systemic mTOR inhibitors, and surgical methods. Cardiac rhabdomyomas have been delineated as the most frequent cardiac tumors in children and the earliest detectable sign of TSC, sometimes delineated prenatally. Cardiac involvement of TSC include single or multiple cardiac rhabadomyxomas that are asymptomatic in most patients. However, they may also cause heart arrhythmias, heart failure, and sudden cardiac death. Nevertheless, due to the tendency for spontaneous decrease or regression, these neoplasms usually do not require treatment. However, in some cases surgical excision or the use of mTOR inhibitors may be necessary. In this chapter we provide a review of both skin and heart findings in the course of TSC, their differentiation, treatment, and prognosis, as we stress the importance for early diagnosis of TSC and, subsequent, an improvement of neurological and cognitive outcome of children with TSC.