Aberrant Cellular Differentiation and Migration in Renal and Pulmonary Tuberous Sclerosis Complex

Abstract

This review is focused on pathways and mechanisms that might provide molecular links between the pathogenesis of renal and pulmonary disease in tuberous sclerosis complex and the pathogenesis of the neurologic manifestations of tuberous sclerosis complex. Tuberous sclerosis complex is an autosomal dominant disorder in which the manifestations can include seizures; mental retardation; autism; benign tumors of the brain, retina, skin, and kidneys; and pulmonary lymphangiomyomatosis. Lymphangiomyomatosis is a life-threatening lung disease affecting almost exclusively young women. Genetic data have demonstrated that the cells giving rise to renal angiomyolipomas, the most frequent tumor type in patients with tuberous sclerosis complex, exhibit differentiation plasticity. Genetic studies have also shown that the benign smooth muscle cells of angiomyolipomas and pulmonary lymphangiomyomatosis have the ability to migrate or metastasize to other organs. These findings indicate that hamartin and tuberin play functional roles in the regulation of cell migration and differentiation. The biochemical pathways responsible for these effects are not yet fully understood but might involve dysregulation of the small guanosine triphosphatase Rho. Similar pathways might contribute to aberrant neuronal differentiation and migration in tuberous sclerosis complex. ( J Child Neurol 2004;19:710—715).