title: Possible prevention of tuberous sclerosis complex lesions.
abstract: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by mammalian target of rapamycin (mTOR) activation and growth of benign tumors. Some TSC lesions, such as cardiac rhabdomyomas and cortical tubers in the brain, occur in fetuses, and some, such as renal angiomyolipomas (AMLs) and skin angiofibromas, develop over years. Recently, the mTOR inhibitor everolimus was shown to be effective in the treatment of subependymal giant cell astrocytomas (a brain tumor) and renal AMLs (kidney tumors) in TSC patients. We present monozygotic twin sisters affected with TSC. Since age 4 years, 1 of the sisters has been treated with everolimus; the other sister received no mTOR inhibitor treatment. After 24-month follow-up, everolimus treatment resulted in a significant brain tumor volume decrease in the treated twin. This child presents no facial angiofibroma, and no renal AMLs. The brain tumor in the nontreated sister is stable in size, but in the meantime, she has developed significant facial angiofibroma and renal AMLs. This observation indicates that early mTOR inhibition in TSC patients may prevent the development of TSC lesions and alter the natural history of the disease.
authors.affiliation: Department of Science, The Children's Memorial Health Institute, Warsaw, Poland. k.kotulska@czd.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kotulska
authors.forename: Julita
authors.initials: J
authors.lastname: Borkowska
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jozwiak
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D004200:Diseases in Twins / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D000068338:Everolimus; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008134:Long-Term Care; D020125:Mutation, Missense / Q000235:genetics; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics*; D014430:Twins, Monozygotic
chemical_list: D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; C486009:TESC protein, human; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: SEGA; everolimus; mTOR; prevention; renal AML; skin lesions; tuberous sclerosis complex