A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis

Table 3

Other types of syndactyly with a unique pathway of pathogenesis or with an undetermined pathogenesis.

Type of syndactyly	Animals or humans	Gene mutation/knockout	Proposed pathogenesis as per our literature review
Poland syndrome (OMIM 173800)	Humans	—	Unique pathway: vascular insult to the subclavian artery during the 19^th embryonic stage
Shaker syndactyly	Mice	Fbn2	Fibrillin-Fibulin interactions leading to increased Fgf8 activity (step II)
Type 9 human syndactyly (OMIM 609432) and mice deficient in BhLha9	Humans/mice	Loss-of-function mutations of BHLHA9 and deletion of the murine ortholog Bhlha9	Either through suppression of Notch signaling (step II, see Table 2) or disturbance of the apoptotic signal (step III)
Noggin-null mice	Mice	Nog	The overexpression of Ihh in the interdigital spaces leading to reduced apoptosis (step III)
Sp6 mutant mice	Mice	Sp6	The mild deficiency in Fgf8 leads to overexpression of Fgf4 in the AER resulting in syndactyly
Type 8 human syndactyly (OMIM 309630)	Humans	FGF16	Either via altering the expression of FGF8 or SHH

AER: apical ectodermal ridge.