Assessment of Treatment Outcomes in the Management of Club foot using the Ponseti Technique: A cross-sectional study.

BACKGROUND: The Ponseti technique remains the preferred method for club foot treatment. Although measures of treatment outcomes have been well documented, there is no consensus on the determinants of those outcomes. This study aims to assess treatment outcomes and the factors which can influence treatment outcomes. MATERIALS AND METHODS: This is a cross-sectional study. A total of 472 children representing 748 feet in total were recruited. Patient characteristics such as age at presentation, gender, tenotomy, walking with or without deformity, parental educational status and occupation were documented. Outcomes of care were assessed using indictors such as parents' satisfaction with the outcome of treatment and the patients' ambulation without deformity. The relationships between the determinant factors and these outcomes were explored using multivariable binary logistic regression. RESULTS: Most of the children (69.1%) were aged below 2 years. Brace compliance was very high (89.9%). The pre-treatment average Pirani scores were 3.9 ± 1.8 and 4.3 ± 1.8 for the right and left feet, respectively. Majority (88.3%) of the children achieved ambulation without deformity, whereas most (87%) of the parents were satisfied with the treatment outcomes. In total, parental satisfaction with child's treatment outcomes was lower in parents who were not formally educated odds ratio (OR) = 0.19 (95% confidence interval [CI] 0.08-0.43), but parental satisfaction was lower if the child had higher Pirani score OR = 0.77 (95% CI 0.62-0.96). Children who had more casts applied to the affected foot were more likely to walk without deformity OR = 1.24 (95% CI 1.01-1.52). CONCLUSIONS: This study revealed that treatment outcomes in children with club foot can be determined by some sociodemographic and treatment-related factors.

Investigations and management of complex congenital talipes equinovarus.

Congenital talipes equinovarus (CTEV) is a congenital deformity affecting the feet, commonly idiopathic in nature. We present a previously unreported cause of a non-idiopathic clubfoot and highlight the importance of poor response to initial treatment.A poor response to Ponseti serial casting for CTEV should alert a clinician to the fact that the foot may not be in the 'idiopathic' group and be of a more complex nature. Idiopathic clubfoot should correct with a maximum of eight serial manipulations, cast applications and Achilles tendon tenotomy. If this is not the case, a repeat careful history, full examination, further investigations and review of the treatment method are required.

Clubfoot patients show more anterior-posterior displacement during one-leg-standing and less ankle power and plantarflexor moment during one-leg-hopping than typically developing children.

BACKGROUND: Clubfoot patients show good-to-excellent foot correction after the Ponseti method. Nevertheless, underlying functional problems that limit motor abilities such as one-leg-standing and one-leg-hopping still persist. These restrictions have been proposed to arise due to problems with maintaining balance and the limited force-generating capacity of clubfoot patients. More insight is needed to understand the underlying limiting factors to improve overall motor ability in clubfoot patients. RESEARCH QUESTION: The aim of this study was to determine the differences between clubfoot patients and typically developing children (TDC) in force and balance parameters during walking, one-leg-standing and hopping. METHODS: Three-dimensional motion analysis was performed in 19 TDC and 16 idiopathic Ponseti-treated clubfoot patients between 5-9 years old. Kinematic and kinetic parameters were calculated during walking and one-leg-hopping. To describe the balance parameters, center of pressure (CoP) data was assessed during walking, one-leg-hopping and one-leg-standing. Mean group values were calculated and compared using nonparametric statistical tests. A general linear model with repeated measures was used to determine which activity showed the largest group differences. RESULTS: Clubfoot patients showed lower peak plantarflexor moment and peak ankle power absorption and generation during one-leg-hopping compared to TDC. Furthermore, clubfoot patients showed a lower hop length and velocity than TDC. The difference in peak plantarflexor moment and ankle power between the study groups was larger during one-leg-hopping than during walking. Finally, clubfoot patients showed a higher anterior-posterior CoP range during one-leg-standing. SIGNIFICANCE: Deviations in force parameters seemed to limit one-leg-hopping in clubfoot patients, and impaired anterior-posterior static balance was thought to be the underlying cause of problems with one-leg-standing. Furthermore, one-leg-hopping was more sensitive to distinguish between clubfoot patients and TDC than walking. Individualized physiotherapy targeting static balance and force parameters, with extra emphasis on including eccentric contractions, might improve the overall motor abilities of clubfoot patients.

First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations.

Importance: Use of buprenorphine or methadone to treat opioid use disorder is recommended in pregnancy; however, their teratogenic potential is largely unknown. Objective: To compare the risk of congenital malformations following in utero exposure to buprenorphine vs methadone. Design, Setting, and Participants: This population-based cohort study used health care utilization data from publicly insured Medicaid beneficiaries in the US from 2000 to 2018. A total of 13 360 pregnancies with enrollment from 90 days prior to pregnancy start through 1 month after delivery and first trimester use of buprenorphine or methadone were included and linked to infants. Data were analyzed from July to December 2022. Exposure: A pharmacy dispensing of buprenorphine or a code for administration of methadone in the first trimester. Main Outcomes and Measures: Primary outcomes included major malformations overall and malformations previously associated with opioids (any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, clubfoot, and oral clefts). Secondary outcomes included other organ system-specific malformations. Risk differences and risk ratios (RRs) were estimated comparing buprenorphine with methadone, adjusting for confounders with propensity score overlap weights. Results: The cohort included 9514 pregnancies with first-trimester buprenorphine exposure (mean [SD] maternal age, 28.4 [4.6] years) and 3846 with methadone exposure (mean [SD] maternal age, 28.8 [4.7] years). The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone. After confounding adjustment, buprenorphine was associated with a lower risk of malformations compared with methadone (RR, 0.82; 95% CI, 0.69-0.97). Risk was lower with buprenorphine for cardiac malformations (RR, 0.63; 95% CI, 0.47-0.85), including both ventricular septal defect (RR, 0.62; 95% CI, 0.39-0.98) and secundum atrial septal defect/nonprematurity-related patent foramen ovale (RR, 0.54; 95% CI, 0.30-0.97), oral clefts (RR, 0.65; 95% CI, 0.35-1.19), and clubfoot (RR, 0.55; 95% CI, 0.32-0.94). Results for neural tube defects were uncertain given low event counts. In secondary analyses, buprenorphine was associated with a decreased risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations compared with methadone. These findings were consistent in sensitivity and bias analyses. Conclusions and Relevance: In this cohort study, the risk of most malformations previously associated with opioid exposure was lower in buprenorphine-exposed infants compared with methadone-exposed infants, independent of measured confounders. Malformation risk is one factor that informs the individualized patient decision regarding medications for opioid use disorder in pregnancy.

Talar neck rotation angle in adults with clubfoot deformity: Observed values and intra- and inter-observer reliability using weightbearing CT.

INTRODUCTION: Adults presenting with symptomatic clubfoot represent a challenging cohort of patients. An appreciation of the location and degree of deformities is essential for management. Talar anatomy is often abnormal with varus within the talar neck, however, there are few reproducible methods which quantify talar neck deformity in adults. We describe a technique of assessing talar neck deformity, and report on observed values and intra- / inter-observer reliability. METHODS: This was a single-centre, retrospective study including 96 feet from 56 adult patients with clubfeet (82 feet had clubfoot deformity, 14 were normal). Mean age was 34.3 ± 16.9 years and 31 (55.3%) were male. Weight-bearing CT scans captured as part of routine clinical care were analysed. Image reformats were oriented parallel to the long axis of the talus in the sagittal plane. In the corresponding axial plane two lines were drawn (on separate slices): 1) a line perpendicular to the intermalleolar axis, 2) a line connecting the midpoints of the talar head and narrowest part of the talar neck. The talar neck rotation angle (TNR angle) was the angle formed between these lines. Intraclass correlation coefficients (ICC) were performed for intra- and inter-observer reliability. RESULTS: Mean TNR angle in clubfeet was 27.6 ± 12.2 degrees (95%CI = 25.0 to 30.2 degrees). Mean TNR angle in normal feet was 18.7 ± 5.1 degrees (95%CI = 16.0 to 21.4 degrees) (p < 0.001). The ICC for clubfeet was 0.944 (95%CI = 0.913 to 0.964) for intra-observer agreement, and 0.896 (95%CI = 0.837 to 0.932) for inter-observer agreement. CONCLUSION: This measurement technique demonstrated excellent intra- and inter-observer agreement. It also demonstrated that compared to normal feet, clubfeet had about 9 degrees of increased varus angulation of the talar neck. This technique and data may be used for future research into clubfoot deformity and in planning treatment. LEVEL OF CLINICAL EVIDENCE: 3.

[Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound].

Objective: To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods. Methods: This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was (M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results: The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up (F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score (r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score (r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score (r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion: Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

The Importance of Having a Single, Dedicated Medical Team to Treat Congenital Talipes Equinovarus Using the Ponseti Method: A Retrospective Analysis of Treatment Outcomes After 3 Years of Follow-up.

BACKGROUND: Congenital talipes equinovarus (CTEV) is a relatively common pediatric orthopaedic disorder and a frequent cause of disability in adult populations. The Ponseti method has emerged as the generally preferred for treating children with CTEV. Strict adherence to this technique's basic principles is critical to achieving favorable outcomes. In 2013, our institution decided that every case of pediatric CTEV would be treated by a single dedicated medical team. The present study aimed to compare the treatment outcomes of children with CTEV treated using the Ponseti method in period I (multiple surgeons) versus those in period II (single dedicated team). PATIENTS AND METHODS: We included respectively the children with CTEV treated using the Ponseti method in Geneva University Hospitals' pediatric units from 2007 to 2018. Data on patient demographics, clinical characteristics, and the treatment outcomes were collected. The primary outcome was the number of relapsed feet (treatment failure) after 3 years of follow-up. The 2 periods' outcomes were compared using χ 2 and independent Student t -tests. Run charts were used to report yearly rates of complications, minor and major recurrences, treatment failure, brace noncompliance, and feet that underwent tenotomy. RESULTS: A total of 48 feet (32 patients) and 42 feet (29 patients) in periods I and II were included. The periods showed similar rates for participants' characteristics. The run charts illustrated the overall improvements in treatment outcomes in period II. A total of 8 relapsed feet (5 patients) were reported, all during period I. CONCLUSIONS: Since all the pediatric CTEV patients at our institution began to be treated by a single dedicated medical team, we have observed a decrease in all recurrences and complications and an absence of treatment failure. These results highlight the importance of the continuity of care and strict adherence to the Ponseti method. LEVEL OF EVIDENCE: Level-III Retrospective comparative study.

Neuromuscular Dysfunction in Clubfeet Associated With Constriction Band Syndrome.

INTRODUCTION: Constriction band syndrome (CBS) is a congenital limb anomaly frequently associated with clubfoot. Clubfeet in CBS patients may be associated with peroneal nerve dysfunction in the involved lower extremity; however, the etiology of this neuromuscular dysfunction is not clear. We sought to characterize the distribution of constriction bands on lower extremities with clubfoot and determine if neuromuscular deficit (NMD), defined here as having absent ankle dorsiflexion, was associated with ipsilateral proximal bands. Our secondary aim was to compare the treatment and outcomes of clubfeet with NMD to those without NMD. METHODS: We performed a retrospective review of all patients with CBS and clubfoot presenting to our facility between January 1, 1998 and December 31, 2018. Treatment with the Ponseti method, at least 1 year of follow-up at this facility, and a detailed physical exam describing lower extremity neuromuscular function and the presence and location of constriction bands were required for inclusion in the study cohort. RESULTS: Twenty children with 26 clubfeet were included. Forty-six percent (12/26) of the clubfeet had NMD. Clubfeet with and without NMD had ipsilateral thigh or leg constriction bands at similar rates [42% (5/12) vs. 43% (6/14), P =0.106], and the majority (7/12) of clubfeet with NMD did not have an ipsilateral thigh or leg band. While children with an NMD clubfoot tended toward more casts, relapses, and surgical procedures, these differences did not reach statistical significance. The use of a daytime AFO beyond age four was higher in the NMD clubfeet [58% (7/12) vs. 14% (2/14), P =0.04]. CONCLUSION: Clubfeet with neuromuscular deficits may occur in the absence of proximal ipsilateral constriction bands, suggesting they may be caused by mechanisms other than direct damage from visible constriction bands to underlying nerves. They can also coexist with arthrogrypotic conditions. Clubfeet with an NMD tended toward more casts, relapses, and surgeries than those without NMD, but these differences did not reach statistical significance. These patients often elect long-term use of a daytime AFO.

Prenatal diagnosis of isolated bilateral clubfoot: Is amniocentesis indicated?

INTRODUCTION: The aim of this study is to evaluate the benefit of cytogenetic testing by amniocentesis after an ultrasound diagnosis of isolated bilateral talipes equinovarus. MATERIAL AND METHODS: This multicenter observational retrospective study includes all prenatally diagnosed cases of isolated bilateral talipes equinovarus in five fetal medicine centers from 2012 through 2021. Ultrasound data, amniocentesis results, biochemical analyses of amniotic fluid and parental blood samples to test neuromuscular diseases, pregnancy outcomes, and postnatal outcomes were collected for each patient. RESULTS: In all, 214 fetuses with isolated bilateral talipes equinovarus were analyzed. A first-degree family history of talipes equinovarus existed in 9.8% (21/214) of our cohort. Amniocentesis was proposed to 86.0% (184/214) and performed in 70.1% (129/184) of cases. Of the 184 karyotypes performed, two (1.6%) were abnormal (one trisomy 21 and one triple X syndrome). Of the 103 microarrays performed, two (1.9%) revealed a pathogenic copy number variation (one with a de novo 18p deletion and one with a de novo 22q11.2 deletion) (DiGeorge syndrome). Neuromuscular diseases (spinal muscular amyotrophy, myasthenia gravis, and Steinert disease) were tested for in 56 fetuses (27.6%); all were negative. Overall, 97.6% (165/169) of fetuses were live-born, and the diagnosis of isolated bilateral talipes equinovarus was confirmed for 98.6% (139/141). Three medical terminations of pregnancy were performed (for the fetuses diagnosed with Down syndrome, DiGeorge syndrome, and the 18p deletion). Telephone calls (at a mean follow-up age of 4.5 years) were made to all parents to collect medium-term and long-term follow-up information, and 70 (33.0%) families were successfully contacted. Two reported a rare genetic disease diagnosed postnatally (one primary microcephaly and one infantile glycine encephalopathy). Parents did not report any noticeably abnormal psychomotor development among the other children during this data collection. CONCLUSIONS: Despite the low rate of pathogenic chromosomal abnormalities diagnosed prenatally after this ultrasound diagnosis, the risk of chromosomal aberration exceeds the risks of amniocentesis. These data may be helpful in prenatal counseling situations.

Obesity Increases Risk for Wound Complications After Pediatric Foot Surgery: A Retrospective Cohort Review Using the NSQIP-Pediatric Database.

BACKGROUND: As the incidence of childhood obesity continues to rise, so too does the number of obese children who undergo foot surgery. As the childhood obesity epidemic rolls on, pediatric orthopaedic surgeons will encounter obese patients with even greater frequency. Therefore, a comprehensive understanding of the risks associated with obesity is valuable to maximize patient safety. The purpose of this study is to retrospectively evaluate the relationship between obesity and postoperative outcomes in patients undergoing pediatric foot surgery across multiple institutions using a large national database. METHODS: Pediatric patients who had undergone foot surgery were retrospectively identified using the American College of Surgeons 2012-2017 Pediatric National Surgical Quality Improvement (ACS-NSQIP-Pediatric) database by cross-referencing reconstructive foot-specific CPT codes with ICD-9/ICD-10 diagnosis codes. Center for Disease Control BMI-to-age growth charts were used to stratify patients into normal-weight and obese cohorts. Univariate and multivariate analyses were performed to describe and assess outcomes in obese compared with normal-weight patients. RESULTS: Of the 3924 patients identified, 1063 (27.1%) were obese. Compared with normal-weight patients, obese patients were more often male (64.7% vs. 58.7%; P =0.001) and taller (56.3 vs. 51.3 inches; P <0.001). Obese patients had significantly higher rates of overall postoperative complications (3.01% vs. 1.32%; P =0.001) and wound dehiscence (1.41% vs. 0.59%; P =0.039). Multivariate analysis found that obesity was an independent predictor of both wound dehiscence [adjusted odds ratio (OR)=2.16; 95% CI=1.05-4.50; P =0.037] and surgical site infection (adjusted OR=3.03; 95% CI=1.39-6.61; P =0.005). Subgroup analysis of patients undergoing clubfoot capsular release procedures identified that obese patients had a higher rate of wound dehiscence (3.39% vs. 0.51%; P =0.039) compared with normal-weight patients. In multivariate analysis, obesity was an independent predictor of dehiscence (adjusted OR=5.71; 95% CI=1.46-22.31; P =0.012) in this procedure group. There were no differences in complication rates between obese and normal-weight patients in a subgroup analysis of tarsal coalition procedures or clubfoot tibialis anterior tendon transfer procedures. CONCLUSION: Obese children undergoing foot surgery had higher overall complication rates, wound complications, and surgical site infections compared with children of normal weight. As the incidence of childhood obesity continues to rise, this information may be useful in assessing and discussing surgical risks with patients and their families. LEVEL OF EVIDENCE: III.

Determining the Optimal Treatment for Idiopathic Clubfoot: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clubfoot, or congenital talipes equinovarus deformity, is a common anomaly affecting the foot in infants. However, clinical equipoise remains between different interventions, especially those based on the Ponseti method. The aim of this study was to examine the clinical outcomes of the various interventions for treating idiopathic clubfoot. METHODS: Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and CINAHL were conducted. Randomized controlled trials comparing different interventions, including the Ponseti method, accelerated Ponseti method, Ponseti method with botulinum toxin type A (Botox) injection, Ponseti method with early tibialis anterior tendon transfer (TATT), Kite method, and surgical treatment, were included. Network meta-analyses (NMAs) were conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) reporting guidelines. The primary outcomes were the change in total Pirani score and maximal ankle dorsiflexion. Secondary outcomes were the number of casts, time in casts, and rates of tenotomy, total complications, relapse, adverse events, and additional required major surgery. RESULTS: Eleven randomized controlled trials involving 740 feet were included. According to the SUCRA (surface under the cumulative ranking curve)-based relative ranking, the Ponseti method was associated with the best outcomes in terms of Pirani score changes, maximal ankle dorsiflexion, number of casts, adverse events, and total complications, whereas the accelerated Ponseti method was associated with the best outcomes in terms of time in casts and tenotomy rate. Early TATT ranked best in terms of relapse rate. The Ponseti method with Botox injection was associated with the best outcomes in terms of the need for additional major surgery. CONCLUSIONS: The NMAs suggest that the Ponseti method is the optimal treatment overall, despite potential drawbacks such as longer time in casts and higher rates of tenotomy, relapse, and the need for additional surgery compared with other modified approaches. Therefore, clinicians should consider how treatments can be tailored individually. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Investigating the association between vitamin D dietary intake during pregnancy and incidence of clubfoot in neonates.

AIMS: Talipes equinovarus (clubfoot) is a congenital lower foot deformity that results from a neuromuscular deficiency, but the precise etiology remains elusive. Vitamin D is important for fetal neuromuscular development. In this study, we investigated the association between dietary vitamin D intake during pregnancy and incidence of clubfoot in neonates, since such a question has thus far been overlooked. METHODS: We conducted a secondary analysis of data collected in the United States, between 2007 and 2011 for a case-control study of children born with clubfoot. Participating mothers were interviewed by telephone about dietary and other health and life-style indicators. Exposure to vitamin D was recorded as the average daily intake of dietary vitamin D over a period of 6 months before pregnancy began. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: The dataset included 2667 study participants, of which 663 were cases. Logistic regression showed no significant association between dietary vitamin D or log10 (Vitamin D) intake during pregnancy and incidence of clubfoot in neonates (OR = 1.00, CI = 1.00-1.00, OR = 1.51, CI = 0.83-2.82, respectively). No interaction in the regression model was found between vitamin D and other predictor variables. Results were not confounded by supplement intake of vitamin D during pregnancy. CONCLUSIONS: Results show no evidence of an association between dietary vitamin D intake and incidence of clubfoot in neonates. The lack of association is not confounded by consumption of vitamin D supplements during pregnancy.

Identification of a novel LMX1B nonsense variant associated with congenital talipes equinovarus by prenatal exome sequencing: A case report.

BACKGROUND: Congenital 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. METHODS: Prenatal 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. RESULTS: A 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. CONCLUSIONS: Our 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.

Lethal variant in the C2A domain may cause severe SYT1-associated neurodevelopmental disorder in the newborns.

Synaptotagmin-1 (SYT1) plays a pivotal role in regulating presynaptic processes, including neurotransmitter release. SYT1 variants perturb synaptic vesicle endocytosis and exocytosis, resulting in a series of neurodevelopmental disorders defined as Baker-Gordon syndrome. Herein, we report the case of a newborn with dysmorphic facial appearance, severe hypotonia, poor feeding, gastroesophageal reflux, and an inability to eat and breathe, diagnosed with Baker-Gordon syndrome. A retrospective search was performed on a newborn with Baker-Gordon syndrome. Medical charts were reviewed, with focus on the clinical presentation, diagnostic process, and treatment outcomes. Whole-genome high-throughput DNA sequencing was performed to identify genetic variants. Whole-exome sequencing identified the likely pathogenic variant as SYT1 C.551 T > C(p.V184A). Sanger sequencing results indicated that this variant was a de novo mutation in a conservative site located in the C2A domain of the protein. The patient died at 57 days old because of severe feeding and breathing problems. Our findings of a novel lethal variant in the C2A domain of SYT1 in the youngest patient diagnosed infantile Baker-Gordon syndrome who presented with the most severe hypotonia reported to date expands the spectrum of SYT1- associated neurodevelopmental disorders.

An Approach to Recurrent Clubfoot Deformity in Adolescents.

Even under ideal circumstances, recurrence of infantile clubfoot deformity following the Ponseti method of treatment is to be expected to occur in as many as 20% of patients. When encountered early in childhood, these recurrences are usually amenable to further casting and limited surgery. Creation of a plantigrade foot, however, becomes much more challenging when recurrences present during adolescence and early adulthood. Because of the stiffer nature of these deformities in older patients, the fact that they are often more severe because of varying lengths of neglect, and the often deleterious effects of prior intra-articular surgeries on joint health, a principled approach is recommended for both the assessment of these feet and development of an appropriate treatment plan. In doing so, the surgeon can select the combination of nonsurgical and surgical interventions that allows for as little surgery as possible to create a plantigrade foot while maintaining any motion that is present before treatment. Although no single algorithmic approach can be applied to the variety of deformities and potentially complicating factors that are encountered in treating such patients, an understanding of the utility of preoperative casting, gradual and acute corrective techniques, and the importance of identifying and mitigating deforming forces and tendon imbalance can greatly optimize outcomes.

Fetal congenital talipes equinovarus: genomic abnormalities and obstetric follow-up results.

OBJECTIVE: The etiology of congenital talipes equinovarus (CTEV) is unknown, and the relationship between chromosome microdeletion/microduplication and fetal CTEV is rarely reported. In this study, we retrospectively analyzed fetal CTEV to explore the relationship among the CTEV phenotype, chromosome microdeletion/microduplication, and obstetric outcomes. METHODS: Chromosome karyotype analysis and single nucleotide polymorphism (SNP) array were performed for the 68 fetuses with CTEV. RESULTS: An SNP array was performed for 68 fetuses with CTEV; pathogenic copy number variations (CNVs) were detected in eight cases (11.8%, 8/68). In addition to one case consistent with karyotype analysis, the SNP array revealed seven additional pathogenic CNVs, including three with 22q11.21 microdeletions, two with 17p12p11.2 microduplications, one with 15q11.2 microdeletions, and one with 7q11.23 microduplications. Of the seven cases carrying pathogenic CNVs, three were tested for family genetics; of these, one was de novo, and two were inherited from either the father or mother. In total, 68 fetuses with CTEV were initially identified, of which 66 cases successfully followed-up. Of these, 9 were terminated, 2 died in utero, and 55 were live births. In 9 cases, no clinical manifestations of CTEV were found at birth; the false-positive rate of prenatal ultrasound CTEVdiagnosis was thus 13.6% (9/66). CONCLUSION: CTEV was associated with chromosome microdeletion/microduplication, the most common of which was 22q11.21 microdeletion, followed by 17p12p11.2 microduplication. Thus, further genomic detection is recommended for fetuses with CTEV showing no abnormalities on conventional karyotype analysis.

COL1A1 regulates the apoptosis of embryonic stem cells by mediating the PITX1/TBX4 signaling.

PURPOSE: The purpose of this study is to explore the regulatory function of COL1A1 against the apoptosis of embryonic stem cells (ESCs) and the potential function in congenital talipes equinovarus (CTEV). METHODS: Muscle tissues were collected from 20 children with CTEV and 20 children without CTEV, followed by detecting the expression of COL1A1 using the RT-PCR method. COL1A1 was knocked down in H1 and H9 human ESCs using the RNA interference technology, followed by determining the level of COL1A1, PITX1, TBX4, HOXD10, Fas, FasL, and Bax using the Western blotting assay. RESULTS: COL1A1 was found markedly upregulated in muscle tissues of CTEV children. In H1 and H9 human ESCs, compared to the empty vector, COL1A1, PITX1, TBX4, HOXD10, Fas, FasL, and Bax were found notably downregulated after transfected with the siRNA targeting COL1A1. CONCLUSION: COL1A1 induced the apoptosis of ESCs by mediating the PITX1/TBX4 signaling and might be a potential target for treating CTEV.

[Correction of gait stereotype and reduction of the risk of falling in patients with equinovarus foot placement and central hemiparesis]. / Korrektsiya stereotipa khod'by i snizhenie riska padeniya u bol'nykh s ekvinovarusnoi ustanovkoi stopy pri tsentral'nom gemipareze.

OBJECTIVE: To test a new approach to gait stereotype correction for patients with central hemiparesis with talipes equinovarus. MATERIAL AND METHODS: The study was performed in a group of patients with formed talipes equinovarus and post-stroke hemiparesis. Footwear with orthopaedic elements was offered to the patients. Evaluation of spatial and temporal gait parameters was performed and the risk of falls was assessed. RESULTS: In the process of work, data were obtained confirming the effectiveness of using specialized shoes for equinovarus foot placement. The risk of falling significantly decreased when walking; walking became more symmetrical due to an increase in the anterior extension of the paretic limb. CONCLUSION: Application of this method does not decrease the tone in the paretic limb but optimises the gait stereotype, facilitates the increases of its velocity and decreases the risk of falling.

A single-center, single-blinded, randomized, parallel-group, non-inferiority trial to compare the efficacy of a 22-gauge needle versus a 15 blade to perform an Achilles tendon tenotomy in 244 clubfeet-study protocol.

BACKGROUND: Achilles tendon tenotomy is an integral part of the Ponseti method, aimed at correcting residual equinus and lack of dorsiflexion after correction of the adductus deformity in clubfoot. Percutaneous tenotomy using a number 15 scalpel blade is considered the gold standard, resulting in excellent results with minimal complications. The use of a large-bore needle to perform Achilles tendon tenotomies has been described in literature, but a large-scale randomized controlled trial is currently lacking. In this trial, we aim to show the non-inferiority of the needle tenotomy technique compared to the gold standard blade tenotomy technique. METHODS: We will randomize 244 feet into group A: needle tenotomy or group B: blade tenotomy. Randomization will be done using a block randomization with random block sizes and applying a 1:1 allocation to achieve an intervention and control group of the exact same size. Children will be evaluated at 3 weeks and 3 months post-tenotomy for primary and secondary clinical outcomes. The primary clinical outcome will be the range of dorsiflexion obtained the secondary clinical outcomes will be frequency of minor and major complications and Pirani score. The non-inferiority margin was set at 4°, and thus, the null hypothesis of inferiority of the needle technique will be rejected if the mean difference between both techniques is less than 4°. The statistical analysis will use a multi-level mixed effects linear regression model for the primary outcomes and a multi-level mixed effects logistic regression model for the secondary clinical outcomes. The physician performing the evaluations post-tenotomy will be the only one blinded to group allocation. TRIAL REGISTRATION: This trial was registered prospectively with ClinicalTrials.gov registration number: NCT04897100 on 21 May 2021.