Genetic Overview of Syndactyly and Polydactyly

Summary: Syndactyly and polydactyly—respectively characterized by fused and supernumerary digits—are among the most common congenital limb malformations, with syndactyly presenting at an estimated incidence of 1 in 2,000–3,000 live births and polydactyly at a frequency of 1 in approximately 700–1,000 live births. Despite their relatively regular manifestation in the clinic, the etiologies of syndactyly and polydactyly remain poorly understood because of their phenotypic and genetic diversity. Further, even though concrete knowledge of genotypic links has been established for some variants of syndactyly and polydactyly, there appears to be no single comprehensive published summary of all syndromic and nonsyndromic syndactyly and polydactyly presentations, and there is decidedly no resource that maps all syndromic and nonsyndromic syndactylies and polydactylies to their genetic bases. This gap in the literature problematizes comprehensive carrier screening and prenatal diagnosis and complicates novel diagnostic attempts. This review thus attempts to collect all that is known about the genetic bases of syndromic and nonsyndromic syndactylies and polydactylies, as well as to highlight the dactyly manifestations for which no genetic bases are as yet known. Then, having established a summation of existing and missing knowledge, this work briefly outlines the diagnostic techniques that a genetics-reinforced understanding of syndactyly and polydactyly could inform.