We observed the cases of two young women who both developed esophageal and perineal tumors successively. The esophageal component usually is the first manifestation. Esophagectomy, with or without gastrectomy is generally required. The genital affection involves the periclitoridian region, the minora and majora labia. Tracheobronchial localization is less common, but it may be lethal due to bronchospasm. An association between diffuse leiomyomatosis and Alport syndrome is not fortuitous. Recently, molecular biology has enabled to understand the combination of the two pathologies by showing the presence of a deletion on adjacent X chromosome genes, COL4A5 and COL4A6, which are involved in the synthesis of type IV collagen fibres. Leiomyomatosis and Alport syndrome are transmitted as X-linked dominant traits. Women with diffuse leiomyomatosis transmit Alport syndrome. An antenatal diagnosis can be proposed for such patients.