A systematic review of association studies of common variants associated with idiopathic congenital talipes equinovarus (ICTEV) in humans in the past 30 years.
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ABSTRACT:
SUBMITTER: Yong BC
PROVIDER: S-EPMC4923008 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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A systematic review of association studies of common variants associated with idiopathic congenital talipes equinovarus (ICTEV) in humans in the past 30 years.
Yong Bi-Cheng BC Xun Fu-Xing FX Zhao Lan-Juan LJ Deng Hong-Wen HW Xu Hong-Wen HW
SpringerPlus 20160627 1
The genetic cause of idiopathic congenital talipes equinovarus (ICTEV) is largely unknown. We performed a systematic review to describe the findings from 21 studies that have examined the genetic variants related to ICTEV, and to evaluate the quality of reporting. We found that ICTEV was positively associated with Hox family genes, collagen family genes, GLI3, N-acetylation genes, T-box family genes, apoptotic pathway genes, and muscle contractile family genes. Negative and controversial results ...[more]
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Project description:BACKGROUND:Also known as clubfoot, idiopathic congenital talipes equinovarus (ICTEV) is the most common pediatric deformity and occurs in 1 in every 1000 live births. Even though it has been widely researched, the etiology of ICTEV remains poorly understood and is often described as being based on a multifactorial genesis. Genetic and environmental factors seem to have a major role in the development of this disease. Thus, the aim of this review is to analyze the available literature to document the current evidence on ICTEV etiology. METHODS:The literature on ICTEV etiology was systematically reviewed using the following inclusion criteria: studies of any level of evidence, reporting clinical or preclinical results, published in the last 20 years (1998-2018), and dealing with the etiology of ICTEV. RESULTS:A total of 48 articles were included. ICTEV etiology is still controversial. Several hypotheses have been researched, but none of them are decisive. Emerging evidence suggests a role of several pathways and gene families associated with limb development (HOX family; PITX1-TBX4), the apoptotic pathway (caspases), and muscle contractile protein (troponin and tropomyosin), but a major candidate gene has still not been identified. Strong recent evidence emerging from twin studies confirmed major roles of genetics and the environment in the disease pathogenesis. CONCLUSIONS:The available literature on the etiology of ICTEV presents major limitations in terms of great heterogeneity and a lack of high-profile studies. Although many studies focus on the genetic background of the disease, there is lack of consensus on one or multiple targets. Genetics and smoking seem to be strongly associated with ICTEV etiology, but more studies are needed to understand the complex and multifactorial genesis of this common congenital lower-limb disease.
| S-EPMC6104023 | biostudies-literature
Project description:BACKGROUND:Treatment of idiopathic congenital talipes equinovarus (CTEV) is challenging for pediatric orthopedic surgeons. The Ponseti method is an effective protocol for treatment due to its technique of manipulation, casting, and limited surgery. Plaster casting is an essential component of the Ponseti method. In this report, we describe a new brace that was developed for use in the treatment of clubfoot in newborns instead of a plaster cast. METHODS:This retrospective study was performed in two orthopedic medical centers. Between January 2011 and October 2013, 89 newborns with CTEV (131?ft) underwent corrective treatment using fixation braces in the experiment group (E-group) in our hospital, and 107 newborns with CTEV (141?ft) underwent plaster casting in the control group (C-group) in another medical center. All patients were treated according to the Ponseti method after the application of the inclusion and exclusion criteria. Plaster casts were applied to patients in the C-group. The patients in the E-group received the custom-made polyaxial fixation braces instead of plaster casts. Prospective follow-up was performed for a mean duration of 36?months. The efficacy of the treatment was assessed using Pirani's scoring system. Chi-squared and independent t tests were used for statistical analyses. RESULTS:In the E-group, 85 patients (125?ft) achieved good appearance within 3?months of treatment initiation (average, 1.7?months). Four patients (6?ft) required percutaneous Achilles tenotomy. Seven patients developed sores during treatment because of improper brace application, but all sores healed without scarring with timely treatment. In the C-group, 96 patients (123?ft) achieved good appearance within 3?months of treatment initiation (average, 1.6?months). Eleven patients (18?ft) required percutaneous Achilles tenotomy. Twenty-one feet developed sores during treatment because of plaster cast pressure on the dorsum of the feet. Sixteen sores healed without scarring with timely treatment, and 5?ft had obvious scars. The overall mean Pirani scores 1 year after treatment were 0.26?±?0.06 in the E-group and 0.25?±?0.03 in the C-group, and the Pirani scores 3 years after treatment were 0.23?±?0.05 in the E-group and 0.22?±?0.03 in the C-group. There were significant differences in the percutaneous Achilles tenotomy and skin sores but no significant difference in the Pirani scores between these two groups. CONCLUSIONS:Our results showed that the new polyaxial fixation brace used in this study was an effective tool for the corrective treatment of CTEV in newborns. We propose the use of this brace as an alternative treatment for newborns.
| S-EPMC6625020 | biostudies-literature
Project description:BackgroundIdiopathic congenital talipes equinovarus (CTEV) is the commonest form of clubfoot. Its exact cause is unknown, although it is related to limb development. The aim of this study was to quantify the anatomy of the muscle, subcutaneous fat, tibia, fibula and arteries in the lower legs of teenagers and young adults with CTEV using 3D magnetic resonance imaging (MRI), and thus to investigate the anatomical differences between CTEV participants and controls.Methodology/principal findingsThe lower legs of six CTEV (2 bilateral, 4 unilateral) and five control young adults (age 12-28) were imaged using a 3T MRI Philips scanner. 5 of the CTEV participants had undergone soft-tissue and capsular release surgery. 3D T1-weighted and 3D magnetic resonance angiography (MRA) images were acquired. Segmentation software was used for volumetric, anatomical and image analysis. Kolmogorov-Smirnov tests were performed. The volumes of the lower affected leg, muscle, tibia and fibula in unilateral CTEV participants were consistently smaller compared to their contralateral unaffected leg, this was most pronounced in muscle. The proportion of muscle in affected CTEV legs was significantly reduced compared with control and unaffected CTEV legs, whilst proportion of muscular fat increased. No spatial abnormalities in the location or branching of arteries were detected, but hypoplastic anomalies were observed.Conclusions/significanceCombining 3D MRI and MRA is effective for quantitatively characterizing CTEV anatomy. Reduction in leg muscle volume appears to be a sensitive marker. Since 5/6 CTEV cases had soft-tissue surgery, further work is required to confirm that the treatment did not affect the MRI features observed. We propose that the proportion of muscle and intra-muscular fat within the lower leg could provide a valuable addition to current clinical CTEV classification. These measures could be useful for clinical care and guiding treatment pathways, as well as treatment research and clinical audit.
| S-EPMC3559654 | biostudies-literature
Project description:BACKGROUND:Congenital talipes equinovarus (CTEV) is a common birth defect that causes severe deformities of one or both feet. Genetics have been proven to play a key role in the risk of CTEV. Our study aimed to evaluate the genetic susceptibility of common variants in the SOX9 gene to CTEV in a Han Chinese population. METHODS:In this study, we recruited 2,205 study participants, including 692 CTEV patients and 1513 healthy controls. A total of seven selected single-nucleotide polymorphisms (SNPs) within the SOX9 gene were genotyped, and environmental variables, including maternal smoking and alcoholic drinking habits, were assessed. In addition, bioinformatics analyses were performed to explore the potential biological functions of the associated SNPs. RESULTS:The SNP rs73354570 was identified to be significantly associated with the risk of CTEV (OR = 1.53, P = 2.11 × 10-5), and the C allele was associated with an increased risk of CTEV. A dose-dependent pattern could be observed in genotypic analyses. The OR for individuals with AC genotypes was 1.37 (95% CI 1.09-1.71), and the OR for individuals with CC homozygotes was 1.47 (95% CI 1.18-1.82). Further analyses identified that rs73354570 is located within a region of multiple binding proteins, including CEBPB and POLR2A, which suggested that this SNP was also part of genetic motifs that are found within several cell types. CONCLUSION:Our results provide evidence supporting the important role of the SOX9 gene in the contribution to the risk of CTEV.
| S-EPMC7376870 | biostudies-literature
Project description:IntroductionIdiopathic congenital talipes equinovarus (CTEV) is the most common congenital limb deformity. Non-operative intervention using the Ponseti method has shown to be superior to soft tissue release and has become the gold standard for first-line treatment. However, numerous deviations from the Ponseti protocol are still reported following incomplete correction or deformity relapse. Significant variation in treatment protocols and management is evident in the literature. Reducing geographical treatment variation has been identified as one of The James Lind Alliance priorities in children's orthopaedics. For this reason, the British Society of Children's Orthopaedic Surgery (BSCOS) commissioned a consensus document to form a benchmark for practitioners and ensure consistent high quality care for children with CTEV.Methods and analysisThe consensus will follow an established Delphi approach aiming at gaining an agreement on the items to be included in the consensus statement for the management of primary idiopathic CTEV up to walking age. The process will include the following steps: (1) establishing a steering group, (2) steering group meetings, (3) a two-round Delphi survey aimed at BSCOS members, (4) final consensus meeting and (5) dissemination of the consensus statement. Degree of agreement for each item will be predetermined. Descriptive statistics will be used for analysis of the Delphi survey results.Ethics and disseminationNo patient involvement is required for this project. Informed consent will be assumed from participants taking part in the Delphi survey. Study findings will be published in an open access journal and presented at relevant national and international conferences. Charities and associations will be engaged to promote awareness of the consensus statement.
| S-EPMC8413928 | biostudies-literature
Project description:BACKGROUND: Idiopathic congenital talipes equinovarus (CTEV) is a common developmental foot disorder, the aetiology of which remains largely unknown. Some aspects of the epidemiology suggest the possibility of aetiologically distinct subgroups. Previous studies consider CTEV as a homogenous entity which may conceal risk factors in particular subgroups. We investigate evidence for aetiologically distinct subgroups of CTEV. METHODS: Parents of 785 probands completed a postal questionnaire. Family pedigrees were compiled by telephone. Case-only analysis was used to investigate interactions between risk factors and sex of the proband, CTEV laterality and CTEV family history. RESULTS: The male:female ratio was 2.3:1, 58% of probands were affected bilaterally and 11% had a first-second degree family history. There were modest interactions between family history and twin births (multivariate case - only odds ratio [ORca] = 3.87, 95%CI 1.19-12.62) and family history and maternal use of folic acid supplements in early pregnancy (ORca = 0.62, 95%CI 0.38-1.01); and between sex of the proband and maternal alcohol consumption during pregnancy (female, positive history and alcohol consumed: ORca = 0.33, 95%CI 0.12-0.89). Previous reports of an interaction between maternal smoking and family history were not confirmed. Relatives of female probands were affected more often than relatives of male probands. CONCLUSIONS: These results provide tentative evidence for aetiologically distinct CTEV subgroups. They support the 'Carter effect', suggesting CTEV develops though a multifactorial threshold model with females requiring a higher risk factor 'load', and suggest areas where future aetiological investigation might focus. Large multi-centre studies are needed to further advance understanding of this common condition.
| S-EPMC3080359 | biostudies-other
Project description:QuestionWhat is the intra and inter-rater reliability and concurrent validity of the weight-bearing lunge test within a Congenital Talipes Equinovarus population?DesignTest retest design for reliability and validity. The measure was taken, following preconditioning of the participants, using distance from wall, angle at distal posterior tibia using a digital inclinometer and the iPhone level function, twice by each rater. The raters included a clinician, clinician in training and a parent/carer.Outcome measuresWeight bearing lunge test as a measure of ankle dorsiflexion.ResultsTwelve children aged 5-10 years were eligible to participate and consented, along with their parents. Intra-reliability of distance measures for all raters were good to excellent (ICC clinician 0.95, ICC training clinician 0.98 and ICC parent 0.89). Intra-rater reliability of the iPhone for all raters was good (ICCs > 0.751) and good to excellent for the inclinometer (ICC clinician 0.87, ICC training clinician 0.90). Concurrent validity between the clinician's and parents distance measure was also high with ICC of 0.899. Inter-rater reliability was excellent for distance measure (ICC = 0.948), good for the inclinometer (ICC = 0.801) and moderate for the iPhone (ICC = 0.68). Standard error of measurement ranged from 0.70-2.05, whilst the minimal detectable change ranged from 1.90-5.70.ConclusionThe use of the WBLT within this CTEV population has demonstrated good to excellent reliability and validity amongst clinicians, clinicians in training and parents/carers, supporting its use as an assessment measure of dorsiflexion range of motion. There is support for parents/carers to use the WBLT at home as a monitoring assessment measure which may assist with early detection of a relapse.Trial registrationUniversity of South Australia's ethics committee (ID: 201397); Women's and Children's Hospital ethics committee (AU/1/4BD7310).
| S-EPMC7792513 | biostudies-literature
Project description:BackgroundCongenital talipes equinovarus (CTEV) is a rotational foot deformity that affects muscles, bones, connective tissue, and vascular or neurological tissues. The etiology of CTEV is complex and unclear, involving genetic and environmental factors. Nail-patella syndrome is an autosomal dominant disorder caused by variants of the LIM homeobox transcription factor 1 beta gene (LMX1B, OMIM:602575). LMX1B plays a key role in the development of dorsal limb structures, the kidneys, and the eyes, and variants in this gene may manifest as hypoplastic or absent patella, dystrophic nails, and elbow and iliac horn dysplasia; glomerulopathy; and adult-onset glaucoma, respectively. This study aimed to identify pathogenic variants in a fetus with isolated talipes equinovarus diagnosed by ultrasound in the second trimester, whose father exhibited dysplastic nails and congenital absence of bilateral patella.MethodsPrenatal whole-exome sequencing (WES) of the fetus and parents was performed to identify the genetic variant responsible for the fetal ultrasound abnormality, followed by validation using Sanger sequencing.ResultsA novel heterozygous nonsense variant in exon 6 of LMX1B (c.844C>T, p.Gln282*) was identified in the fetus and the affected father but was not detected in any unaffected family members. This nonsense variant resulted in a premature termination codon at position 282, which may be responsible for the clinical phenotype through the loss of function of the gene product.ConclusionsOur study indicating that a fetus carrying a novel nonsense variant of LMX1B (c.844C>T, p.Gln282*) can exhibit isolated talipes equinovarus, which expands the LMX1B genotypic spectrum and is advantageous for genetic counseling.
| S-EPMC10767578 | biostudies-literature
Project description:<p>Isolated clubfoot or idiopathic talipes equinovarus (ITEV) is one of the five most common birth defects, affecting approximately 4,000 newborns each year in the US. While the orthopedic care of these children has improved, long-term problems persist and the health care costs are significant. Studies suggest that clubfoot is a complex disorder with segregation analyses and family studies indicating that genetic factors play an important etiologic role in the development of clubfoot. Only one environmental factor, maternal smoking during pregnancy, has been implicated. We postulate that a small number of genes account for a substantial fraction of clubfoot and that these genes can be identified in a defined population. The challenge now is to identify the genetic loci and, later, the effect of environmental exposures. To accomplish this task, it is important to have a well-defined population and the methodology to detect linkage with and without association. Towards these goals, we have identified and characterized multiplex clubfoot families, including two large clubfoot families, a resource which is among the largest ITEV populations in existence. We will perform a high-density SNP genome scan (GWAS) on our clubfoot dataset to identify chromosomal regions that may harbor clubfoot genes with subsequent interrogation of these regions and candidate genes. We are in a position with our unique clubfoot population and with the methodology in place to undertake this study. The study phases are: 1) continued ascertainment of multiplex and simplex families and 2) GWAS and characterization of identified chromosomal regions and candidate genes. The results of this study will provide data essential to the identification of the gene(s) contributing to the clubfoot phenotype. Identification of high-risk genotypes can lead to the development of prevention programs in selected populations and may suggest gene-based prevention strategies.</p>
| phs000314.v1.p1 | EGA
Project description:This paper aims to assess the status of scientific literature on talipes equinovarus (TEV) published from Pakistan, to get an insight into the trend in knowledge over the years, and to highlight study gaps in this area. A detailed review of published literature was conducted from November 2019 to January 2020. 'Talipes/congenital talipes', 'clubfoot/congenital clubfoot', 'talipes equinovarus /congenital talipes equinovarus' AND 'Pakistan' were used as key terms. Different search engines, PubMed, PakMediNet, ScienceDirect, Embase and Google Scholar were utilized to retrieve articles. A total of 63 articles were retrieved. The hotspot of TEV research in Pakistan has been its treatment and management. Over the years, treatment trend has shifted from operative to conservative; Ponseti method is predominantly employed. Hospital-based studies focusing on pediatric patients are common while population-based studies are devoid. In majority of cohorts, there is preponderance of male patients, idiopathic and unilateral cases. There is, however, scarcity of basic research on the prevalence, etiology, risk factors, clinical heterogeneity, associated anomalies, genetics, and molecular diagnostics of TEV. In conclusion, prudent scientific evidence is required for any policy-making and relevant public health action. Hence, large scale population-based studies are required for a broader overview and understanding the clinical spectrum of TEV.
| S-EPMC7501030 | biostudies-literature