Given that TIMP-3 interacts with fibulin-3 [61] and is thought to be activated by WT1 [97], it may be that part of the increased risk of IH conferred by these variants lies in an alteration of TIMP-3 regulation that shifts the equilibrium between ECM degrading and synthesising enzymes and perturbs connective tissue homeostasis. This evidence concerns the gene TIMP3 and isolated hemihyperplasia.