Characterization of Patients With Tuberous Sclerosis Complex, Lymphangioleiomyomatosis and Angiomyolipoma

Tuberous Sclerosis Complex (TSC) is a multisystemic autosomal dominant disease that is characterized by the development of benign neoplasms in brain, kidney, lung, skin and heart. TSC is caused by mutations in TSC1 and/or TSC2 genes, which encode, respectively, hamartin and tuberin, that are involved in the regulation of cell proliferation, cell cycle and protein synthesis. Most patients exhibit dermatological, renal, neurological and pulmonary (lymphangioleiomyomatosis, LAM) manifestations. Neurological involvement include subependymal nodules, subependymal giant cell astrocytomas and cortical tubers. LAM is characterized by the proliferation of LAM cells around the airways, blood vessels and lymphatics, which result in vascular and airway obstruction and cyst formation. The most frequent TSC manifestation in the kidney is the development of angiomyolipomas (AML). Dermatologic lesions represent the most common manifestations of TSC, mainly hypomelanotic macules and facial angiofibromas. The most significant functional implication of the tuberin-hamartin complex is its regulatory role upon the mammalian target of rapamycin (mTOR) pathway. Mutations in TSC1 or TSC2 lead to increased mTOR activity and favor tumor development and growth. All lesions associated with TSC, sporadic LAM and sporadic AML share a common molecular pathogenesis, based on TSC1/TSC2 mutations and mTOR hyperactivity. Up to date, TSC patients have been followed in separated medical services in our institution, according to their predominant phenotype. The current knowledge, however, suggest that the ideal follow up of such patients should be conducted in an integrated fashion among the specialties associated with the main disease manifestations. Experts in TSC from each of these areas have recently created a TSC/LAM/AML integrated program in the University of São Paulo Medical Center, and his project will be initiated with the generation of an integrated TSC/LAM/AML registry, which intends not only to clinically characterize this patient population but also to document the employed treatment modalities. Once this first goal is achieved, clinical trials are planned to be performed. The central aim of this observational study is to clinically characterize the TSC/LAM/AML subject population followed and referred to the University of São Paulo Medical Center. Specific aims: To characterize the pulmonary, the neurological, the renal and the dermatologic phenotypes of this patient population.

Sex

All

Inclusion Criteria:

* All patients with TSC, LAM (sporadic or associated with TSC) or AML (sporadic or associated with TSC or with LAM) followed at Hospital das Clínicas, University of São Paulo Medical School will be included in the proposed study. Patients of all ages will participate in the study.

Exclusion Criteria:

* There is no exclusion criteria.

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