Prevalence and Associations of Depression in Parents of Children With Congenital Talipes Equinovarus: A Single-Centre Study.

INTRODUCTION: Congenital talipes equinovarus (CTEV) is a congenital deformity that requires weekly visits to the hospital for manipulation and corrective cast application, followed by an intensive bracing regimen requiring multiple visits to the hospital spread over the years. Parents of children with clubfoot are known to undergo a range of negative emotions. The objective of this study was to identify the prevalence of depression and the factors associated with depression in parents of children with idiopathic CTEV. METHODS: This cross-sectional study consecutively enrolled 190 parents of children with idiopathic CTEV undergoing treatment at King George Medical University. Parents with conditions that preclude the assessment of mental status were not included. These conditions include a history of head injury or psychiatric illness, parents with ongoing treatment of psychiatric illness, ongoing chronic illness, chronic neurological disease, and parents with clinically established intellectual disability. Information was recorded on certain parent-related characteristics and certain child-related characteristics. Parent-related information included age and sex of the parent, religion, area of residence, number of children in the family, degree of perceived social support (using the Multidimensional Scale of Perceived Social Support, MSPSS), level of education, socio-economic status, depression subscale score of DASS 21 (Depression, Depression Anxiety, and Stress Scale -21), chronic pain (visual analogue scale, VAS), family history of clubfoot or depression, and level of stress caused by a major life event during the past year using the Presumptive Stressful Life Event Scale (PSLES). Child-related information included the sex of the child, phase of treatment (casting or bracing), limb involvement (unilateral or bilateral), relapse of the deformity, and Pirani score of the deformity. Bivariate analysis and logistic regression were used to identify factors associated with a score ≥10 on the depression subscale of DASS 21. RESULTS: One hundred forty-five subjects were males (76.3%). The mean age of the enrolled parents was 28.47±4.89 years. The mean score on the depression subscale of DASS-21 was 4.87±6.3. Thirty-two parents (16.8%) had a score of ≥10 on the depression subscale of the DASS-21. On bivariate analysis, female sex, being Hindu, having studied up to class 12th, relapse, MSPSS score, and PSLES score were found to be associated with a score ≥10 on the depression subscale of the DASS-21. On logistic regression, female sex, lack of graduate education and above, and MSPSS scores were found to be significantly associated with a score of ≥10 on the depression subscale of the DASS 21 score. CONCLUSION: The prevalence of depression in parents of children with idiopathic clubfoot was 16.8%. Female gender, lack of college education, and the level of perceived social support (MSPSS) are independently associated with a score ≥10 on the depression subscale of DASS 21. We recommend screening parents of children with clubfoot and referring those with abnormal scores to a psychiatrist for a confirmed diagnosis.

A thorough analysis of data on the correlation between COL9A1 polymorphisms and the susceptibility to congenital talipes equinovarus: a meta-analysis.

BACKGROUND: Congenital talipes equinovarus (CTEV) is a prevalent pediatric deformity with a multifactorial etiology. The objective of this meta-analysis was to explore the association between genetic variations in COL9A1 and the susceptibility to CTEV. METHODS: A comprehensive analysis of pertinent literature released before November 15, 2023, in electronic bibliographic databases was carried out. The importance of the connection was clarified through odds ratios (ORs) with 95% confidence intervals (CIs), utilizing random or fixed-effects models depending on study heterogeneity. Statistical analysis was executed using Comprehensive Meta-Analysis software (Version 4.0). RESULTS: A total of eight case-control studies involving 833 CTEV patients and 1280 healthy individuals were included in the analysis. Among these, four studies investigated the rs1135056 variant, encompassing 432 CTEV cases and 603 controls; two studies examined the rs35470562 variant, with 189 CTEV cases and 378 controls; and two studies explored the rs592121 variant, including 212 CTEV cases and 299 controls. The results revealed a significant association between the rs1135056 and rs35470562 polymorphisms in the COL9A1 gene, suggesting an increased risk of CTEV in the overall population. Conversely, no such association was found for the rs592121 variant. CONCLUSION: Our findings reveal a substantial association between the genetic variants COL9A1 rs1135056 and rs35470562 and susceptibility to CTEV. Conversely, the variant rs592121 did not exhibit any corresponding link. However, the limitations imposed by the small study population have compromised the statistical reliability and generalizability of the results.

Duration and outcome of orthotic treatment in children with clubfoot - a four-year follow-up national register study of Swedish children born between 2015 and 2017.

BACKGROUND: The Ponseti method for treating clubfoot consists of initial treatment with serial casting accompanied by achillotenotomy if needed, followed by the maintenance phase including treatment with a foot abduction orthosis (FAO) for at least four years. This study aimed to examine the duration, course, and outcome of orthotic treatment in children with clubfoot. METHODS: 321 children with clubfoot, born between 2015 and 2017, registered in the Swedish Pediatric Orthopedic Quality Register (SPOQ), were included in this prospective cohort study. Data on deformity characteristics and orthotic treatment were extracted. For children with bilateral clubfoot, one foot was included in the analysis. RESULTS: Of the 288 children with isolated clubfoot, 274 children (95.5%) were prescribed an FAO, and 100 children (35%) changed orthosis type before 4 years of age. Of the 33 children with non-isolated clubfoot, 25 children (76%) were prescribed an FAO, and 21 children (64%) changed orthosis type before 4 years of age. 220 children with isolated clubfoot (76%), and 28 children with non-isolated clubfoot (84%) continued orthotic treatment until 4 years of age or longer. Among children with isolated clubfoot, children ending orthotic treatment before 4 years of age (n = 63) had lower Pirani scores at birth compared to children ending orthotic treatment at/after 4 years of age (n = 219) (p = 0.01). It was more common to change orthosis type among children ending orthotic treatment before 4 years of age (p = 0.031). CONCLUSIONS: The majority of children with clubfoot in Sweden are treated with an FAO during the maintenance phase. The proportion of children changing orthosis type was significantly greater and the Pirani score at diagnosis was lower significantly among children ending orthotic treatment before 4 years of age. Long-term follow-up studies are warranted to fully understand how to optimize, and individualize, orthotic treatment with respect to foot involvement and severity of deformity. LEVEL OF EVIDENCE: II.

Assessing the Influence of Age, Weight, and Pirani Score on the Number of Casts During the Initial Phase of Clubfoot Treatment Using the Ponseti Method: A Prospective Study.

Background: Clubfoot, also known as congenital talipes equinovarus is a prevalent childhood ailment that, if untreated, can lead to long-term discomfort and impairment. The Ponseti technique, aimed at achieving corrected foot positioning, is widely accepted. This study investigated the influence of clubfoot severity (Pirani score), patient age, and initial manipulation and casting weight on the overall number of casts needed for effective treatment. Methods: A prospective study was carried out involving 40 idiopathic clubfoot patients where manipulation and casting were performed following the Ponseti method. Patient age, weight, and foot Pirani score were evaluated concerning the total number of casts needed to achieve 70° of abduction. Results: The majority of participants were male infants aged 4-6 months, with a median age of 4.5 months. Half of them weighed between 3.00 and 4.99 kg at their first hospital visit, with a median weight of 3.20 kg. Bilateral clubfoot involvement was common (57.5%). Children with Pirani HFCS 2.0-3 often required percutaneous tenotomy (87.5%, p value 0.05). On average, patients needed 5 casts (range 3-9). The mean total Pirani scores were 4.71 for the right foot and 4.61 for the left foot. The study reported a positive correlation between higher total Pirani scores and the required number of casts. Conclusions: The Pirani scoring system is highly accurate in assessing clubfoot severity and predicting treatment success. It emerged as the single most significant predictor for both the total number of casts and the need for percutaneous tenotomy.

TRAPPC11-CDG muscular dystrophy: Review of 54 cases including a novel patient.

The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD). We reviewed the phenotype of all reported individuals with TRAPPC11-opathies, including an additional Mexican patient with novel compound heterozygous missense variants in TRAPPC11 (c.751 T > C and c.1058C > G), restricted to the Latino population. In these 54 patients muscular dystrophy signs are common (early onset muscle weakness, increased serum creatine kinase levels, and dystrophic changes in muscle biopsy). They present two main phenotypes, one with a slowly progressive LGMD with or without GDD/ID (n = 12), and another with systemic involvement characterized by short stature, GDD/ID, microcephaly, hypotonia, poor speech, seizures, cerebral atrophy, cerebellar abnormalities, movement disorder, scoliosis, liver disease, and cataracts (n = 42). In 6 of them CMD was identified. Obstructive hydrocephaly, retrocerebellar cyst, and talipes equinovarus found in the individual reported here has not been described in TRAPPC11 deficiency. As in previous patients, membrane trafficking assays in our patient showed defective abnormal endoplasmic reticulum-Golgi transport as well as decreased expression of LAMP2, and ICAM-1 glycoproteins. This supports previous statements that TRAPPC11-opathies are in fact a congenital disorder of glycosylation (CDG) with muscular dystrophy.

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.

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.

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.

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.

Comprehensive Rehabilitation of Charcot Foot With Equinovarus Deformity: A Case Report.

Charcot neuroarthropathy is the destruction of the bones and joints caused by underlying neuropathy, trauma, and disturbances in bone metabolism. Modern health care and surgical options now include limb salvage. An acquired or congenital foot deformity is the equinovarus deformity, also known as clubfoot or talipes equinovarus. The foot is fixed in plantarflexion (equinus), deviates toward its center (varus), and is rotated upward so that it rests on its outside (supination) in this condition. In another way, the foot turns axially outward while pointing downward and inward. Charcot neuroarthropathy generally occurs due to diabetes, but in this case, it occurs due to trauma and leads to a traumatic congenital talipes equinovarus deformity. A 38-year-old male patient complained of right foot pain and an inability to walk. Two years ago, he was involved in an accident that left him with a right leg injury. He was eventually diagnosed with a mid-shaft tibia-fibula fracture and underwent surgery with nailing. But one month ago, he again met with an accident and was diagnosed with Charcot's foot and equinovarus deformity. He returned to Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi, Wardha, Maharashtra, for further management. K-wire was applied for the fixation of Charcot foot with equinovarus deformity. Further on, rehabilitation was started to restore mobility, regain full range of motion and develop muscle strength.

Conversations About Congenital Clubfoot: Investigating How Parents Share Information About a Structural Diagnosis With Their Children.

Background and objective Clubfoot is a common congenital musculoskeletal condition that is treated with manipulation and casting in the first few weeks of life, followed by bracing that extends into early childhood. While children typically do not recall treatment with Ponseti casting in infancy, childhood treatment and monitoring may result in a sense of heightened awareness. In light of this, this study explores how parents share information about clubfoot diagnosis and guide their children in understanding the importance of treatment. Methods Parents of clubfoot children aged 5-18 years were eligible to participate. Primary recruitment was done through social media via Facebook clubfoot support groups. Participants who gave consent completed an electronic survey and were invited to take part in a semi-structured interview to share additional experiences. Significant themes elicited from study interviews were analyzed along with survey responses. Results Survey responses were received from 74 parents, and 23 participated in the semi-structured interview. Of note, 91% of parents indicated discussing clubfoot with their children, beginning at a median age of three years. The age at which parents first discussed clubfoot with their child was significantly earlier for those who "strongly agree" that their children understand their condition versus those who "agree". Although 68% of parents indicated that receiving guidance from their orthopedic provider would be helpful for these discussions, only 18% noted receiving direct advice. Recurrent themes across interviews included being open and honest about the children's diagnosis and treatment, aiding the children in taking ownership of their diagnosis, and validating emotional responses throughout treatment.  Conclusions This study provides valuable insights into initiating conversations with children about structural diagnoses like congenital clubfoot. Recurrent themes from conversations with families provide information on helpful strategies to encourage early discussions about clubfoot diagnosis and treatment to aid children in taking ownership of their diagnosis.

The Effectiveness of Physical Therapy Intervention in a Seven-Year-Old Child With Congenital Talipes Equinovarus: A Case Report.

Congenital talipes equinovarus (CTEV), a prevalent congenital anomaly, is characterized by the backward bending of the hindfoot, the inward turning of the midfoot, and the turning or tilting of the front foot. The likelihood of experiencing clubfoot is higher in males and among firstborn offspring. Both genetic and environmental elements are recognized as factors that play a role in the occurrence of this developmental irregularity. It is diagnosed clinically because the abnormality has been visible since childhood, where one or both feet point downward and inward. If the deformity is not addressed, tarsal bones and joints will stiffen over time, further causing an inability to walk and stand, causing additional limb deformities. Late presentations are typical in less developed nations because of a lack of awareness, access to care, or a holdup in referral. We have a case of a seven-year-old spastic cerebral palsy (CP) male child with congenital talipes equinovarus. While assessing, we found visible deformities at the knee and ankle joints. Wedge osteotomy and Achilles tendon lengthening surgery were performed. Probably, extensive soft tissue surgery is the best option for treating clubfoot. A physical therapist may use stretching, proprioceptive neuromuscular facilitation (PNF), joint mobilization, and joint compression to enhance the foot's alignment, mobility, and range of motion (ROM) to keep the joint in the correct position. Physical therapy greatly reduced stiffness. The physiotherapy treatment plan we used was highly beneficial in enhancing the patient's quality of life, increasing his level of independence, and enhancing his participation in his activities of daily living (ADLs).

[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.

Incidence and prevalence of congenital clubfoot in Apulia: a regional model for future prospective national studies.

BACKGROUND: Congenital clubfoot is a fairly common and severe congenital malformation, most often of idiopathic origin. A smaller percentage of cases is related to chromosomal abnormalities and genetic syndromes. It is estimated that 0.5/1000 newborns are affected worldwide, with a male to female ratio of 2:1 and greater distribution in developing countries (80%). The "European Surveillance of Congenital Anomalies (EUROCAT)" reported clubfoot prevalence in European newborns, but data regarding Italy are missing or poor. We aim to provide detailed data on clubfoot incidence according to the Apulian Regional Registry on Congenital Malformations and to report current knowledge on clubfoot genetic factors. METHODS: We extrapolated data from the Regional Registry of Congenital Malformations to evaluate incidence and prevalence of congenital clubfoot in Apulia, Italy over a period of four years (2015-2018). We also performed a narrative review focusing on genetic mutations leading to congenital clubfoot. RESULTS: Over the period from 2015 to 2018 in Apulia, Italy, 124,017 births were recorded and 209 cases of clubfoot were found, accounting for an incidence rate of 1.7/1,000 and a prevalence rate of 1.6/1,000. Six families of genes have been reported to have an etiopathogenetic role on congenital clubfoot. CONCLUSIONS: Incidence and prevalence of congenital clubfoot in Apulia, Italy, are comparable with those reported in the other Italian regions but higher than those reported in previous studies from Europe. Genetic studies to better classify congenital clubfoot in either syndromic or isolated forms are desirable.

Prenatal diagnosis and genetic etiology analysis of talipes equinovarus by chromosomal microarray analysis.

BACKGROUND: With the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by Chromosomal Microarray Analysis (CMA). METHODS: This retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n = 55) and complex group (n = 76) according to structural anomalies. RESULTS: Among the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis (P < 0.05). SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group (karyotype: P < 0.05; SNP array: P < 0.05). The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant (P > 0.05). Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities. CONCLUSION: Fetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE.

Conventional Versus Accelerated Ponseti in the Management of Cases of Idiopathic Clubfoot: A Systematic Review and Meta-Analysis.

This study aimed to compare the outcomes of the accelerated and standard Ponseti method for clubfoot pathology by constructing a systematic review and meta-analysis of relevant randomized controlled trials and nonrandomized comparative studies. A systematic search was conducted to identify the relevant studies through PubMed, Google Scholar, and Cochrane depending on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The keywords used included "accelerated" AND "standard" AND "Ponseti" AND "clubfoot" AND "Congenital Talipes Equinovarus" AND "CTEV" AND "prospective comparative design" AND "randomized trial." We conducted this analysis among 13 studies that met the criteria adopted in this review where eight studies were prospective comparative studies, and five studies were randomized prospective comparative studies which were published in the period between 2015 and 2022. Statistically, accelerated Ponseti showed superior impact over standard Ponseti considering the duration of treatment (22.53 days vs. 40.61 days, p<0.001). No significant difference was reported between the two methods considering final Pirani score (0.64 vs. 0.56, p=0.194), number of casts (5.23 vs. 5.25, p=0.425), rate of tenotomy (66.2% vs. 63.1%, OR=1.246, 95% CI: 0.86-1.80, p=0.245), relapse rate (9.51% vs. 8.54%, OR=1.126, 95% CI: 0.68-1.86, p=0.642) and complication rate (14.4% vs. 13.1%, OR=1.130, 95% CI: 0.58-2.19, p=0.717). We concluded that the accelerated Ponseti method could achieve comparable efficacy to the standard method in terms of post-procedure Pirani score, tenotomy rate, relapse rate, complications rate, and number of casts needed by the patients with advantage of requiring shorter duration of treatment which is associated with more patient's compliance.

Trends in congenital clubfoot prevalence and co-occurring anomalies during 1994-2021 in Denmark: a nationwide register-based study.

BACKGROUND: Congenital talipes equinovarus (clubfoot) is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. Herein, we used publicly available data to ascertain liveborn infants with clubfoot delivered in Denmark during 1994-2021, and to classify co-occurring congenital anomalies, estimate annual prevalence, and compare clubfoot occurrence with maternal smoking rates, a commonly reported risk factor. Characterizing this nationwide, liveborn cohort provides a population-based resource for etiopathogenic investigations and life course surveillance. METHODS: This case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,315,282 liveborn infants delivered during 1994-2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources. RESULTS: Infants most often presented with nonsyndromic clubfoot (isolated = 88.6%; MCA = 11.4%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45-1.58) for isolated and 0.19 (CI 0.17-0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained relatively stable during the study period, despite marked decreases in population-based maternal smoking rates. CONCLUSIONS: From 1994 to 2021, prevalence of nonsyndromic clubfoot in Denmark was relatively stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates, providing some support for the suspected multifactorial etiopathogenesis of this anomaly. This nationwide, liveborn cohort, ascertained and clinically characterized using publicly available data from the Danish Biobank Register, provides a population-based clinical and biological resource for future etiopathogenic investigations and life course surveillance.

A Rare Presentation of Bifid Tibialis Anterior Tendon in a Case of Idiopathic Congenital Talipes Equinovarus.

Introduction: Idiopathic congenital talipes equinovarus (CTEV) is one of the most extensively researched topics for decades. It has been associated with various musculoskeletal anomalies which maybe bony, vascular or involving the ligaments and muscles which may have a direct or indirect impact on its pathoanatomy. This report describes an unusual presentation of a bifid tibialis anterior tendon (TAT) in a case of CTEV. This is the first report of this kind in the literature to the best of our knowledge. Case Report: A 4-year-old female presented with bilateral relapsed CTEV with dynamic supination previously treated with standard Ponseti protocol. The patient was treated with TAT transfer on the left side with a rare presentation of a bifid TAT where both the slips of the tendon were transferred to dorsum of the foot onto the lateral cuneiform. Conclusion: When treating a patient of CTEV surgically, it is important to consider the possibility of a bifid TAT which is a rare musculoskeletal association. It is recommended to carefully dissect TAT to prevent under correction of the deformity in case either one of the tendon slips remains attached to its original site.

De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease-associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).