The Alport syndrome-diffuse leiomyomatosis association can be defined as a hereditary disease of type IV collagen combining features of Alport syndrome (hematuric nephropathy, deafness and ocular abnormalities: anterior lenticonus, maculopathy) and leiomyomatosis involving oesophagus (diffuse type), tracheobronchial tree, and genitals (only in women). This entity is transmitted as an X-linked dominant trait. Mutations of both the COL4A5 and COL4A6 genes, located head to head in Xq22 encoding the alpha 5 and alpha 6(IV) chains are responsible for the abnormalities. Molecular studies have shown deletions of the 5' end of both COL4A5 and COL4A6 including the intergenic region. The breakpoint in COL4A6 is always located within intron 2. Immunohistochemistry has shown significant alterations of basement membranes in the kidney and esophageal leiomyomas. Leiomyomas lack alpha 5 and alpha 6(IV) chains, fibronectin and laminin beta 1 chains in the muscle basement membranes where they are normally expressed. The tumors also show myocyte anomalies: irregular expression of the alpha 5 integrin subunits, and disorganization of actin and desmin filaments. It is hypothesized that a third as yet unknown gene, situated within the large intron 2 in a critical 90 kb region, is responsible for the smooth muscle proliferation. Abnormalities of the basement membranes could destabilize interactions between muscular cells and the extracellular matrix.