Pathogenesis of cataracts in patients with Lowe's syndrome

Based on our morphologic and ultrastructural studies, we suggest that the characteristic lens opacities in Lowe's syndrome result from a genetic defect in the lens cells. This defect manifests early in embryogenesis, and the progression of the lens opacities is related to both the inherent genetic abnormality and the prevailing extralenticular environment. The defective formation and subsequent degeneration of the primary posterior lens fibers account for their loss and for the flattened, discoid, or ring-shaped cataract. The other findings, such as anterior polar cataract, subcapsular fibrous plaque, capsular excrescences, bladder cells, and posterior lenticonus are not necessarily specific for Lowe's syndrome. We believe that the pathogenesis of Lowe's cataract can be explained by Lyon's hypothesis, which implies that, very early in embryogenesis (at the stage of the primitive streak), one of the two X chromosomes in females is deactivated. We consider the high incidence of lens opacities in female carriers to be due to this random deactivation. In male probands, however, all lens cells are affected, since there is no normal X chromosome to nullify the effect of the Lowe gene.