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The Journal of the American Academy of... May 2021Pediatric foot polydactyly presents in a wide variety of deformities from single extra digits attached only by a narrow soft-tissue connection to complex central foot... (Review)
Review
Pediatric foot polydactyly presents in a wide variety of deformities from single extra digits attached only by a narrow soft-tissue connection to complex central foot duplications with tarsal bone duplication. The goal of surgical reconstruction is a stable, mobile, pain-free foot with five cosmetically appealing toes that allows for normal footwear and painless ambulation. This review covers the incidence, genetics and embryology, classification, presentation and natural history, physical examination, radiographic assessment, and surgical intervention for all types of foot polydactyly.
Topics: Child; Foot; Foot Deformities, Congenital; Humans; Polydactyly; Toes; Walking
PubMed: 33443388
DOI: 10.5435/JAAOS-D-20-00983 -
Current Opinion in Obstetrics &... Apr 2017
Topics: Brain Diseases; Female; Fetal Therapies; Humans; Oligohydramnios; Polydactyly; Pregnancy; Ultrasonography, Prenatal; Zika Virus; Zika Virus Infection
PubMed: 28253207
DOI: 10.1097/GCO.0000000000000352 -
Progress in Biophysics and Molecular... Sep 2018We present a cellular automaton-based model for threshold behaviors in vertebrate digit patterning and polydactyly formation. The rules of the model follow classical... (Review)
Review
We present a cellular automaton-based model for threshold behaviors in vertebrate digit patterning and polydactyly formation. The rules of the model follow classical reactor-diffusion algorithms. Yet it is not physical diffusion that is taken as the required natural agent but the propagation of cellular states, which can be represented by the same differential equations. The bistable cellular states in the model correspond to mesenchymal limb bud cells that can be either "on" or "off" for the cartilage differentiation pathway. Simulation runs demonstrate that reaction rate and cell number have the most decisive influence on the number of digit-like cell activation patterns. Threshold-based effects can generate supernumerary activation stripes via de novo condensation, stabilized bifurcation, and free floaters. All three behaviors are consistent with processes in natural polydactyly formation. It is argued that these effects are rooted in cell-based behaviors, not in gene regulation or globally diffusing morphogens. Our model suggests that the origin of discrete character states, such as individual digits, is a consequence of an additive cell state variable with a normal distribution that is transformed by a growth function with Turing behaviors into discontinuous phenotypic units. We discuss the application of this type of autopod patterning to the mutational, developmental, experimental, and evolutionary occurrences of polydactyly. The model provides a refinement of the previous Hemingway model for digit novelty and supports Turing type pattern formation in the vertebrate limb.
Topics: Animals; Cell Count; Humans; Models, Biological; Polydactyly
PubMed: 29739620
DOI: 10.1016/j.pbiomolbio.2018.04.007 -
Medicine Dec 2022This study collects what is known about the inheritance underpinnings of syndromic and non-syndromic polydactylies and highlights dactyly presentations with unknown... (Review)
Review
OBJECTIVE
This study collects what is known about the inheritance underpinnings of syndromic and non-syndromic polydactylies and highlights dactyly presentations with unknown genetic roots. This review summarizes the current information and genetics-enhanced understanding of polydactyly.
BACKGROUND
There is a frequency of 0.37 to 1.2 per 1000 live births for polydactyly, which is also known as hyperdactyly. It is characterized by the presence of extra fingers. Polydactyly is caused by a failure in limb development, specifically the patterning of the developing limb bud. The phenotypic and genetic variability of polydactyly makes its etiology difficult to understand. Pre-axial polydactyly, central polydactyly (axial), and postaxial polydactyly are all examples of non-syndromic polydactyly (ulnar). An autosomal dominant disorder with varying penetrance that is mostly passed down via limb development patterning abnormalities.
METHOD
A comprehensive search of MEDLINE/PubMed and other databases was followed by an evaluation of the relevant papers, with a particular focus on those published between 2000 and 2022.
RESULTS
Of 747 published article related to Polydactyly from MEDLINE/PubMed search, 43 were from the last 10 years and were the focus of this review.
CONCLUSION
Polydactyly is one of the most frequent congenital hand malformations. PAP is more common than PPD, whereas central polydactyly is very uncommon.
Topics: Humans; Polydactyly; Fingers; Toes
PubMed: 36550802
DOI: 10.1097/MD.0000000000032060 -
Neonatal Network : NN 2016Polydactyly, also known as hyperdactyly, is a common congenital limb defect, which can present with various morphologic phenotypes. Apart from cosmetic and functional... (Review)
Review
Polydactyly, also known as hyperdactyly, is a common congenital limb defect, which can present with various morphologic phenotypes. Apart from cosmetic and functional impairments, it can be the first indication of an underlying syndrome in the newborn. Usually, it follows an autosomal dominant pattern of inheritance with defects occurring in the anteroposterior patterning of limb development. Although many mutations have been discovered, teratogens have also been implicated in leading to this anomaly, thus making it of multifactorial origin. There are three polydactyly subtypes (radial, ulnar, and central), and treatment options depend on the underlying feature.
Topics: Fingers; Genetic Markers; Humans; Infant, Newborn; Mutation; Polydactyly; Syndrome
PubMed: 27194607
DOI: 10.1891/0730-0832.35.3.135 -
Clinical Genetics Jan 2023Polydactyly or polydactylism, also known as a hyperdactyly, is a congenital limb defect with various morphologic phenotypes. Apart from physical and functional... (Review)
Review
Polydactyly or polydactylism, also known as a hyperdactyly, is a congenital limb defect with various morphologic phenotypes. Apart from physical and functional impairments, the presence of polydactyly is an indication of an underlying syndrome in the newborn. Usually, it follows as an autosomal dominant/recessive inheritance pattern with defects in the limb development's anteroposterior patterning. Although mutations in several genes have been associated with polydactyly; however, the exact underlying cause, pathways, and disease mechanisms are still unexplored, thus making it of multi-factorial origin. Polydactyly is divided into three subtypes; radial, ulnar, and central polydactyly. So far, 11 loci (PAPA1-PAPA11) and seven human genes have been reported to cause non-syndromic postaxial polydactyly in humans, including the ZNF141, GLI3, IQCE, GLI1, FAM92A1, KIAA0825, and DACH1. In this review, we discuss emerging evidences of clinical and molecular characterization of polydactyly types in term of the involvement of newly associated genes and loci for non-syndromic postaxial polydactyly, and how these might impact our understanding of the genetic mechanisms and molecular etiology involved in the cause of polydactyly.
Topics: Infant, Newborn; Humans; Polydactyly
PubMed: 36071556
DOI: 10.1111/cge.14224 -
The Orthopedic Clinics of North America Jan 2016Physicians who specialize in pediatric orthopedics and hand surgery frequently encounter congenital hand abnormalities, despite their relative rarity. The treating... (Review)
Review
Physicians who specialize in pediatric orthopedics and hand surgery frequently encounter congenital hand abnormalities, despite their relative rarity. The treating physician should be aware of the associated syndromes and malformations that may, in some cases, be fatal if not recognized and treated appropriately. Although these congenital disorders have a wide variability, their treatment principles are similar in that the physician should promote functional use and cosmesis for the hand. This article discusses syndactyly, preaxial polydactyly and post-axial polydactyly, and the hypoplastic thumb.
Topics: Fingers; Hand Deformities, Congenital; Humans; Orthopedic Procedures; Polydactyly; Postoperative Care; Surgical Flaps; Syndactyly; Thumb; Treatment Outcome
PubMed: 26614930
DOI: 10.1016/j.ocl.2015.08.015 -
Current Opinion in Pediatrics Feb 2023Polydactyly presents with variable extent of duplication and may involve preaxial/radial (hand)/medial (foot), postaxial/ulnar (hand)/lateral (foot) or central... (Review)
Review
PURPOSE OF REVIEW
Polydactyly presents with variable extent of duplication and may involve preaxial/radial (hand)/medial (foot), postaxial/ulnar (hand)/lateral (foot) or central duplication. This review will summarize recent advancements in the surgical management of this common entity.
RECENT FINDINGS
Modifications to classification systems aim to help guide surgical management of polydactyly. Attempts have been made at quantifying preoperative angulation of the duplicated digits to minimize the chance of residual or recurrent deformity after surgical reconstruction. As a result, consideration should be given to the need for soft tissue correction vs. osteotomy to optimize the clinical outcome. On-top plasty is an option that may be beneficial in 'unequal' preaxial polydactyly, where neither duplicate is preferred on its own.
SUMMARY
Polydactyly is one of the most common congenital anomalies in the hands and feet. Determination of surgical intervention often begins with classification systems that exist, which primarily separate these into preaxial, postaxial, and central. Referral for surgical consideration is indicated, given the management is often surgical.
Topics: Humans; Polydactyly; Thumb; Plastic Surgery Procedures; Osteotomy
PubMed: 36412268
DOI: 10.1097/MOP.0000000000001204 -
Developmental Dynamics : An Official... Apr 2022Primary cilia are dynamic compartments that regulate multiple aspects of cellular signaling. The production, maintenance, and function of cilia involve more than 1000... (Review)
Review
Primary cilia are dynamic compartments that regulate multiple aspects of cellular signaling. The production, maintenance, and function of cilia involve more than 1000 genes in mammals, and their mutations disrupt the ciliary signaling which manifests in a plethora of pathological conditions-the ciliopathies. Skeletal ciliopathies are genetic disorders affecting the development and homeostasis of the skeleton, and encompass a broad spectrum of pathologies ranging from isolated polydactyly to lethal syndromic dysplasias. The recent advances in forward genetics allowed for the identification of novel regulators of skeletogenesis, and revealed a growing list of ciliary proteins that are critical for signaling pathways implicated in bone physiology. Among these, a group of protein kinases involved in cilia assembly, maintenance, signaling, and disassembly has emerged. In this review, we summarize the functions of cilia kinases in skeletal development and disease, and discuss the available and upcoming treatment options.
Topics: Animals; Cilia; Ciliopathies; Homeostasis; Mammals; Polydactyly; Proteins
PubMed: 34582081
DOI: 10.1002/dvdy.426 -
Nature Feb 2024Enhancers control the location and timing of gene expression and contain the majority of variants associated with disease. The ZRS is arguably the most well-studied...
Enhancers control the location and timing of gene expression and contain the majority of variants associated with disease. The ZRS is arguably the most well-studied vertebrate enhancer and mediates the expression of Shh in the developing limb. Thirty-one human single-nucleotide variants (SNVs) within the ZRS are associated with polydactyly. However, how this enhancer encodes tissue-specific activity, and the mechanisms by which SNVs alter the number of digits, are poorly understood. Here we show that the ETS sites within the ZRS are low affinity, and identify a functional ETS site, ETS-A, with extremely low affinity. Two human SNVs and a synthetic variant optimize the binding affinity of ETS-A subtly from 15% to around 25% relative to the strongest ETS binding sequence, and cause polydactyly with the same penetrance and severity. A greater increase in affinity results in phenotypes that are more penetrant and more severe. Affinity-optimizing SNVs in other ETS sites in the ZRS, as well as in ETS, interferon regulatory factor (IRF), HOX and activator protein 1 (AP-1) sites within a wide variety of enhancers, cause gain-of-function gene expression. The prevalence of binding sites with suboptimal affinity in enhancers creates a vulnerability in genomes whereby SNVs that optimize affinity, even slightly, can be pathogenic. Searching for affinity-optimizing SNVs in genomes could provide a mechanistic approach to identify causal variants that underlie enhanceropathies.
Topics: Humans; Enhancer Elements, Genetic; Extremities; Gain of Function Mutation; Homeodomain Proteins; Interferon Regulatory Factors; Organ Specificity; Penetrance; Phenotype; Polydactyly; Polymorphism, Single Nucleotide; Protein Binding; Proto-Oncogene Proteins c-ets; Transcription Factor AP-1
PubMed: 38233525
DOI: 10.1038/s41586-023-06922-8