Genetic Overview of Syndactyly and Polydactyly

Abstract

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.

Variant metatarsal morphology causing metatarsal deformation in postaxial polydactyly

“…Polydactyly is a common, congenital condition, characterized by the presence of one or more supernumerary digits, with or without duplication of the corresponding metatarsal or phalanges. [2][3][4][5] It is more common in upper limbs than in lower limbs, right hand than left hand and left foot than right foot. 4 There is tremendous variation in the extent of duplication, ranging from minor cutaneous protuberance, to duplication of a single phalanx, to complete duplication of the digit and metacarpal or metatarsal, and may result in a functional digit.…”

“…It is believed to be an inherited condition, transferred in an autosomal dominant pattern with variable expression and incomplete penetrance. 2,5,6,9 A positive family history has been reported in between 8% and 39% of cases. 5,6,9 Patients with polydactyly may be asymptomatic, although it can result in a significant handicap.…”

“…Polydactyly is a common, congenital condition, characterized by the presence of one or more supernumerary digits, with or without duplication of the corresponding metatarsal or phalanges . It more common in upper limbs than in lower limbs, right hand than left hand and left foot than right foot .…”

“…Pedal polydactyly is one of the most common foot anomalies, accounting for around 45% of congenital foot abnormalities . Its incidence is between 0.3 and 3.6 per 1000 live births, of which postaxial polydactyly comprises up to 87% of cases . It can be present in isolation in a single limb, although it may be bilateral, or associated with upper limb polydactyly, brachydactylia, syndactyly or other genetic syndromes …”

“…Despite its prevalence, the precise aetiology of polydactyly is unknown. It is believed to be an inherited condition, transferred in an autosomal dominant pattern with variable expression and incomplete penetrance . A positive family history has been reported in between 8% and 39% of cases …”