A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis
Embryology of normal web space creation and the genetics of syndactyly in humans and experimental animals are well described in the literature.
In this review, the author offers a 3-step pathway of pathogenesis for syndactyly.
The first step is initiated either by the overactivation of the WNT canonical pathway or the suppression of the Bone Morphogenetic Protein (BMP) canonical pathway.
This leads to an overexpression of Fibroblast Growth Factor 8 (FGF8).
The final step is the suppression of retinoic acid in the interdigital mesenchyme leading to suppression of both apoptosis and extracellular matrix (ECM) degradation, resulting in syndactyly.
Since Fibrillins and Fibulins are both important components of elastic fibers and both are known to interact, the pathogenesis of Sy syndactyly may be investigated to determine if it is through Fibulin1 as a modifier of Fgf8 activity in Step II.
Common Design 