Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent of genetic and molecular techniques, mutations in the TSC1 or TSC2 genes were discovered to be responsible for mTOR overactivation, which is the underlying mechanism of pathogenesis. TSC is a highly heterogenous clinical entity with variable presentations and severity of disease. The brain, heart, skin, eyes, kidneys, and lungs are commonly involved in this syndrome, with neurologic symptoms comprising a significant source of morbidity and mortality. In 2012, the diagnostic criteria for TSC were revised by the International Tuberous Sclerosis Complex Consensus panel, and genetic testing was incorporated into the guidelines. Early detection of cardiac rhabdomyomas or TSC-associated skin lesions can suggest the diagnosis and underlie the importance of clinical vigilance. Animal studies have demonstrated the benefit of using mTOR inhibitors for various symptoms of TSC, and they have been successfully translated into clinical trials with significant improvement in symptom burden. Subependymal giant cell astrocytomas, renal angiomyolipomas, and epilepsy are the three FDA-approved indications in relation to TSC for the use of everolimus, which is a first generation mTOR inhibitor. Rapamycin has been FDA approved for lymphangioleiomyomatosis. Other TSC symptoms that could potentially benefit from this class of medication are currently under investigation. TSC constitutes a unique combination of protean physical symptoms and neurobehavioral abnormalities. TSC associated neuropsychiatric disorders (TAND), including intellectual disability, mood disorders, and autism spectrum disorder, represent significant challenges but remain underdiagnosed and undertreated. The TAND checklist is a useful tool for routine use in the clinical evaluation of TSC patients. A multidisciplinary treatment plan, based on the specific problems and needs of individuals, is the key to management of this genetic condition. Ongoing research studies have been providing promising leads for developing novel mechanistic strategies to address the pathophysiology of TSC.
Highlights
Tuberous sclerosis complex (TSC) is a rare, multisystem, autosomal dominant syndrome characterized by tumorigenesis and is associated with neurologic and behavioral abnormalities
The 2012 International Tuberous Sclerosis Complex Consensus group established the guidelines for evaluation of neuropsychiatric manifestations of TSC, by providing the practitioners with a TSC associated neuropsychiatric disorders (TAND) checklist
Neurologic management Once a diagnosis of TSC is reached, a baseline MRI is recommended to look for the presence of any cortical malformations as tubers, SENs, or subependymal giant cell astrocytomas (SEGAs) [68]
Summary
Tuberous sclerosis complex (TSC) is a rare, multisystem, autosomal dominant syndrome characterized by tumorigenesis and is associated with neurologic and behavioral abnormalities. Common manifestations include cortical tubers, subependymal nodules, subependymal giant cell astrocytomas (Figure 1), seizures, cardiac rhabdomyomas, renal AMLs, retinal hamartomas, pulmonary lymphangioleiomyomatosis (LAM), facial angiofibromas (Figure 2), ash-leaf spots, shagreen patches, intellectual disability, and autism spectrum disorder [1,3]. The protein products of the TSC genes, hamartin and tuber, work together within the same intracellular pathway, which explains why a mutation in either gene can give rise to the same disease.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
