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History of Tuberous Sclerosis Complex History of Tuberous Sclerosis Complex
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Epidemiology Epidemiology
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Clinical Presentation Clinical Presentation
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Diagnostic Criteria Diagnostic Criteria
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Lab Tests Lab Tests
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Differential Diagnosis Differential Diagnosis
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Management and Treatment Management and Treatment
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Course Course
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Genetics, Pathogenesis, and Pathology Genetics, Pathogenesis, and Pathology
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Current Clinical Trials and Future Directions Current Clinical Trials and Future Directions
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References References
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136 Familial CNS Tumor Syndromes: Tuberous Sclerosis
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Published:August 2016
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Abstract
Tuberous sclerosis complex is an autosomal dominant multi-system disease that involves the skin, brain, heart, lungs, and kidneys and is associated with seizures including infantile spasms, intellectual disability, autism and pulmonary and heart disease. Skin lesions can be particularly disfiguring and infantile spasms can be associated with marked cognitive decline. The outlook for patients has improved markedly with the recognition that TSC is caused by upregulation of the mammalian target of rapamycin (mTOR) enzyme, which connects energy needs and supply with cellular and neuronal growth. mTOR is upregulated in TSC because of mutations in hamartin or tuberin, which normally serve as a brake on mTOR. The drug rapamycin is commonly used as an immunosuppressive for patients undergoing kidney transplants; it has also found a new use in patients with TSC. Although the drug is immunosuppressive for non-TSC patients, careful titration of the drug in TSC patients corrects its upregulation but is not particulary immunosuppressive. Additional mTOR inhibitors such as everolimus have been developed and have been shown to be effective for pulmonary disease associated with TSC. Rapamycin in ointment form is dramatically effective in suppressing skin lesions of TSC and studies are underway to test the effect of mTOR inhibitors on seizures, brain tubers, intellect, and features of autism. Infantile spasms associated with TSC are very responsive to vigabatrin.
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