Review Article
A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis
Table 1
Syndactyly in humans classified according to the steps shown in Figure
1.
| Step affected | Gene mutation | Name of syndrome or type of syndactyly as per Malik’s classification (OMIM if available) |
| IA: activation of the WNT canonical signaling or the accumulation of beta catenin | (i) LRP4 | (i) Cenani–Lenz syndrome or type 7a syndactyly (212780) | (ii) APC | (ii) Cenani–Lenz phenotype |
| IB: suppression of the BMP canonical signaling | (i) FMN1 deletions or duplication encompassing GREM1-FMN1 | (i) Cenani–Lenz phenotype or type 7b syndactyly | (ii) ZRS | (ii) Haas (type 4) syndactyly (186200); triphalangeal thumb polysyndactyly syndrome (174500) | (iii) RAB23 | (iii) Carpenter syndrome (201000) | (iv) TWIST1 | (iv) Saethre–Chotzen syndrome (101400) | (v) GLI3 | (v) Greig syndrome (175700) and other GLI3-related syndactyly | (vi) GJA1 | (vi) Johnston–Kirby type 3 syndactyly (186100) |
| II: increased activity of FGF8 | (i) Gain-of-function mutations of FGFR1 or FGFR2 | (i) Pfeiffer (101600), Apert (101200), and Saethre-Chotzen (101400) syndromes. | (ii) FBLN1 | (ii) Debeer type 2b syndactyly (608180) |
| III: suppression of retinoic acid or suppression of apoptosis/matrix degradation | (i) HOXD13 | (i) Vordingborg type 2a syndactyly (186000) and syndactyly type 5 (186300) |
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