Polydactyly and Related Congenital Foot Anomalies

Congenital foot anomalies encompass a spectrum of limb malformations, among which polydactyly is one of the most frequently encountered. Polydactyly refers to the presence of extra toes and may occur in isolation or as part of a broader syndrome. Preaxial polydactyly involves duplication on the medial side of the foot, postaxial on the lateral side and central polydactyly in the middle of the digital series. Extreme manifestations include mirror foot, characterised by a complete medial duplication of rays resembling a mirror image, and diplopodia, in which a partial or complete second foot is attached to the tibia or fibula. Less common anomalies, such as longitudinal epiphyseal bracket, affect bone growth by introducing an aberrant ossification centre that constrains angular development. Genetic regulation of limb patterning has been shown to involve the zone of polarising activity regulatory sequence (ZRS), GLI3 and other cis-regulatory elements, accounting for variability in digit number and morphology across populations. Clinically, these anomalies present challenges in terms of walking ability, footwear fitting and aesthetic concerns, and are managed through individualised surgical planning, informed by radiography, three-dimensional imaging and, increasingly, molecular diagnostics. Global research has emphasised the need for standardised classification, early functional assessment and multidisciplinary care to optimise long-term outcomes and quality of life.

Research from Nature Portfolio

Seminal work has elucidated how duplications of a long-range enhancer, the ZRS, can lead to multiple preaxial supernumerary digits beyond the typical single extra ray. Quantitative analysis in a large familial pedigree demonstrated that increased copy number of the ZRS region promotes the development of more than one redundant digit on the thumb side, underscoring the dose-dependent effect of regulatory sequence variation on limb morphogenesis. This finding has established a paradigm in which enhancer dosage, rather than coding mutations, can drive complex digit duplication phenotypes.

Polydactyly and Related Congenital Foot Anomalies publication trend

The graph below shows the total number of articles in polydactyly and related congenital foot anomalies across all publications each year (not limited to Nature Index journals).

Technical terms

Polydactyly: The congenital presence of more than five digits on a hand or foot.

Preaxial polydactyly: Duplication of one or more digits on the medial (tibial) side of the foot.

Postaxial polydactyly: Duplication of one or more digits on the lateral (fibular) side of the foot.

Central polydactyly: Duplication of digits in the central axis of the foot, between the great and little toes.

Mirror foot: An extreme form of preaxial polydactyly with complete medial duplication of metatarsals and phalanges.

Diplopodia: A rare anomaly in which a partial or complete second foot structure is attached to the lower limb.

ZPA regulatory sequence (ZRS): A limb-specific enhancer controlling SHH gene expression and digit patterning.

Longitudinal epiphyseal bracket: An aberrant secondary ossification centre that extends along a bone shaft, causing angular deformity.

References

1. Longitudinal epiphyseal bracket. Journal of Children's Orthopaedics (2013).
2. Mirror foot: Treatment of three cases and review of the literature. Journal of Children's Orthopaedics (2009).
3. A rare association of deformities with diplopodia, aplasia of the tibia and double fibula: A case report. Journal of Medical Case Reports (2008).
4. Lower Extremity Polydactyly Does Not Disturb Finding One's Feet. The Journal of Foot & Ankle Surgery (2023).
5. ZPA Regulatory Sequence Variants in Chinese Patients With Preaxial Polydactyly: Genetic and Clinical Characteristics. Frontiers in Pediatrics (2022).
6. An increased duplication of ZRS region that caused more than one supernumerary digits preaxial polydactyly in a large Chinese family. Scientific Reports (2016).