Clubfoot is one of the most common musculoskeletal birth deformities worldwide. The prevalence varies among individual countries and populations. There is a lack of nationwide incidence studies in Central Europe. We analyzed the incidence of clubfoot in the Czech Republic over 14 years. Patients born with clubfoot in the Czech Republic were identified using The National Registry of Congenital Anomalies. Demographic data were included. Data from 2000 to 2014 were collected and analyzed regarding gender and regional distribution. The study's chosen time frame was grounded on the condition of the Czech industry. Following extensive transformations in 1989, the industry eliminated highly non-ecological operations with significant environmental impact and related health risks. The incidence of clubfoot during the study period was 1.9 (95% CI 1.8-2.0) per 1000 births; males comprised the majority (59%). The incidence significantly differed among individual regions of the Czech Republic (p < 0.001). The incidence in the Czech Republic was higher than in previous European studies. We found significant regional differences in incidence, which could indicate that there may be exogenous pathogenic factors. For this reason, we plan to follow up our work with an up-to-date study.

• Klíčová slova
• clubfoot, congenital talipes equinovarus, epidemiology, foot deformity, incidence,
• Publikační typ
• časopisecké články MeSH

Our aim was to study the expression of hypoxia-related proteins as a possible regulatory pathway in the contracted side tissue of relapsed clubfoot. We compared the expression of hypoxia-related proteins in the tissue of the contracted (medial) side of relapsed clubfoot, and in the tissue of the non-contracted (lateral) side of relapsed clubfoot. Tissue samples from ten patients were analyzed by immunohistochemistry and image analysis, Real-time PCR and Mass Spectrometry to evaluate the differences in protein composition and gene expression. We found a significant increase in the levels of smooth muscle actin, transforming growth factor-beta, hypoxia-inducible factor 1 alpha, lysyl oxidase, lysyl oxidase-like 2, tenascin C, matrix metalloproteinase-2, matrix metalloproteinase-9, fibronectin, collagen types III and VI, hemoglobin subunit alpha and hemoglobin subunit beta, and an overexpression of ACTA2, FN1, TGFB1, HIF1A and MMP2 genes in the contracted medial side tissue of clubfoot. In the affected tissue, we have identified an increase in the level of hypoxia-related proteins, together with an overexpression of corresponding genes. Our results suggest that the hypoxia-associated pathway is potentially a factor contributing to the etiology of clubfoot relapses, as it stimulates both angioproliferation and fibroproliferation, which are considered to be key factors in the progression and development of relapses.

• MeSH
• hemoglobin - podjednotky MeSH
• hypoxie komplikace   genetika   MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 genetika   MeSH
• pes equinovarus * genetika   MeSH
• recidiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hemoglobin - podjednotky MeSH
• matrixová metaloproteinasa 2 MeSH

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of collagen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, β-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.

• Klíčová slova
• beta-aminopropionitrile (BAPN), collagen, congenital idiopathic Talipes equinovarus, contraction, crosslinking, fibrosis, relapsed clubfoot,
• MeSH
• aminopropionitril farmakologie   MeSH
• fibroblasty účinky léků   MeSH
• kolagen chemie   MeSH
• lidé MeSH
• lysyloxidasa antagonisté a inhibitory   MeSH
• pes equinovarus farmakoterapie   metabolismus   patologie   MeSH
• předškolní dítě MeSH
• reagencia zkříženě vázaná farmakologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminopropionitril MeSH
• kolagen MeSH
• LOX protein, human MeSH Prohlížeč
• lysyloxidasa MeSH
• reagencia zkříženě vázaná MeSH