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Congenital scoliosis (CS) is a type of vertebral malformation for which the etiology remains elusive. The notochord is pivotal for vertebrae development, but its role in CS is still understudied. Here, we generated a zebrafish knockout of ptk7a, a planar cell polarity (PCP) gene that is essential for convergence and extension (C&E) of the notochord, and detected congenital scoliosis-like vertebral malformations (CVMs). Maternal zygotic ptk7a mutants displayed severe C&E defects of the notochord. Excessive apoptosis occurred in the malformed notochord, causing a significantly reduced number of vacuolated cells, and compromising the mechanical properties of the notochord. The latter manifested as a less-stiff extracellular matrix along with a significant reduction in the number of the caveolae and severely loosened intercellular junctions in the vacuolated region. These defects led to focal kinks, abnormal mineralization, and CVMs exclusively at the anterior spine. Loss of function of another PCP gene, vangl2, also revealed excessive apoptosis in the notochord associated with CVMs. This study suggests a new model for CS pathogenesis that is associated with defects in notochord C&E and highlights an essential role of PCP signaling in vertebrae development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Purpose: Scoliosis is a complex spine deformity with direct functional and cosmetic impacts on the individual. The reference standard for assessing scoliosis severity is the Cobb angle which is measured on radiographs by human specialists, carrying interobserver variability and inaccuracy of measurements. These limitations may result in lack of timely referral for management at a time the scoliotic deformity progression can be saved from surgery. We aimed to create a machine learning (ML) model for automatic calculation of Cobb angles on 3-foot standing spine radiographs of children and adolescents with clinical suspicion of scoliosis across 2 clinical scenarios (idiopathic, group 1 and congenital scoliosis, group 2). Methods: We retrospectively measured Cobb angles of 130 patients who had a 3-foot spine radiograph for scoliosis within a 10-year period for either idiopathic or congenital anomaly scoliosis. Cobb angles were measured both manually by radiologists and by an ML pipeline (segmentation-based approach-Augmented U-Net model with non-square kernels). Results: Our Augmented U-Net architecture achieved a Symmetric Mean Absolute Percentage Error (SMAPE) of 11.82% amongst a combined idiopathic and congenital scoliosis cohort. When stratifying for idiopathic and congenital scoliosis individually a SMAPE of 13.02% and 11.90% were achieved, respectively. Conclusion: The ML model used in this study is promising at providing automated Cobb angle measurement in both idiopathic scoliosis and congenital scoliosis. Nevertheless, larger studies are needed in the future to confirm the results of this study prior to translation of this ML algorithm into clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aims to evaluate the long-term outcomes of one-stage posterior hemivertebra resection and short segment fusion with pedicle screw fixation in children with thoracolumbar congenital early-onset scoliosis (TLCEOS). It specifically investigates the durability of spinal correction and the incidence of complications over an average follow-up of 8.97 years., Methods: A retrospective review was conducted on 32 patients treated at a tertiary scoliosis referral center from April 2003 to December 2019. Inclusion criteria were thoracolumbar hemivertebra (T11-L1), treatment via posterior hemivertebra resection and short segment fusion (≤ 5 segments), age under 10 years at surgery, and a follow-up of at least 5 years. Exclusions included idiopathic, syndromic, or neuromuscular scoliosis. Data on demographics, surgical procedures, and radiographic outcomes were collected, and clinical outcomes were evaluated using the Scoliosis Research Society-22 (SRS-22) questionnaire. Statistical analysis was performed using SPSS and R software., Results: The study included 32 patients (22 males, 10 females) with a mean age of 5.00 ± 2.42 years at surgery and an average follow-up of 8.97 ± 2.81 years. On average, 3.47 ± 1.11 segments were fused. The main curve corrected from 38.64° ± 14.12° preoperatively to 9.06° ± 7.29° postoperatively, with a final correction rate of 61%. Significant improvements were observed in the SRS-22 domains of Appearance and Satisfaction with Treatment. There were 17 complications, including neurological, pulmonary, and mechanical issues, with some cases requiring revision surgery., Conclusions: One-stage posterior hemivertebra resection and short segment fusion with pedicle screw fixation effectively correct TLCEOS long-term, offering significant improvements in patient appearance and satisfaction, with a manageable complication profile., (© 2024. The Author(s).)

Background: Congenital scoliosis (CS) is a spinal disorder caused by genetic-congenital vertebral malformations and may be associated with other congenital defects or may occur alone. It is genetically heterogeneous and numerous genes contributing to this disease have been identified. In addition, CS has a wide range of phenotypic and genotypic variability, which has been explained by the intervention of genetic factors like modifiers and environment genes. The aim of the present study was to determine the possible cause of CS in a Tunisian patient and to examine the association between mtDNA mutations and mtDNA content and CS., Methods: Here we performed Whole-Exome Sequencing (WES) in a patient presenting clinical features suggestive of severe congenital scoliosis syndrome. Direct sequencing of the whole mitochondrial DNA (mtDNA) was also performed in addition to copy number quantification in the blood of the indexed case. In silico prediction tools, 3D modeling and molecular docking approaches were used., Results: The WES revealed the homozygous missense mutation c.512A > G (p.H171R) in the TBXT gene. Bioinformatic analysis demonstrated that the p.H171R variant was highly deleterious and caused the TBXT structure instability. Molecular docking revealed that the p.H171R mutation disrupted the monomer stability which seemed to be crucial for maintaining the stability of the homodimer and consequently to the destabilization of the homodimer-DNA complex. On the other hand, we hypothesized that mtDNA can be a modifier factor, so, the screening of the whole mtDNA showed a novel heteroplasmic m.10150T > A (p.M31K) variation in the MT-ND3 gene. Further, qPCR analyses of the patient's blood excluded mtDNA depletion. Bioinformatic investigation revealed that the p.M31K mutation in the ND3 protein was highly deleterious and may cause the ND3 protein structure destabilization and could disturb the interaction between complex I subunits., Conclusion: We described the possible role of mtDNA genetics on the pathogenesis of congenital scoliosis by hypothesizing that the presence of the homozygous variant in TBXT accounts for the CS phenotype in our patient and the MT-ND3 gene may act as a modifier gene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Early recognition is crucial for occult spinal dysraphism associated with congenital spinal deformities. There is limited literature available on its occurrence in congenital scoliosis and kyphosis in the Indian population., Methods: Our study involved a retrospective review of 247 children who presented at a single centre. We analyzed their demographics and clinical and radiological findings, which included the type of deformity, its location, vertebral anomaly, Cobb angle, and MRI findings. The deformities were categorized as congenital scoliosis or congenital kyphosis with failure of formation, failure of segmentation, or both., Results: A total of 247 cases were examined (congenital scoliosis-229, congenital kyphosis-18). The average age was seven years (range 0.8 to 19 years, SD 4.6). The mean Cobb angle at presentation in the congenital scoliosis group was 49.4° (range 8 to 145°, SD 23.77) for those with abnormal MRI and 42.45° (range 5 to 97°, SD 20.09) for those with normal MRI. For the congenital kyphosis group, the mean K angle at presentation was 47.7° (range 14 to 110°, SD 33.33) for those with abnormal MRI and 47.36° (range 15 to 70°, SD 16.63) for those with normal MRI. Abnormal MRI results were observed in 130 of the patients (congenital scoliosis-53.7%, congenital kyphosis-38.8%). The highest incidence of abnormal MRI findings was observed in the failure of segmentation (66.6%) and mixed (65%) types. Deformities in the dorsal region had the highest incidence (61.9%). The most common dysraphism instances were diastematomyelia and tethered cord. There was a significant correlation between type of deformity and presence of dysraphism., Conclusion: This is the largest case series of congenital scoliosis and kyphosis reported from India. We found a high incidence of occult spinal dysraphism as compared to other published series. Occult spinal dysraphism is more common in the thoracic region. Diastematomyelia followed by tethered cord was the most common anomaly observed. We recommend MRI screening of whole spine and craniovertebral junction., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Purpose: Spinal osteotomies are often essential in the treatment of congenital scoliosis. Risk factors for bleeding in these patients needing extracavitatory approaches, especially hidden blood loss, are sparsely investigated. We aimed to investigate the bleeding characteristics and hidden blood loss in paediatric patients undergoing spinal osteotomies for congenital scoliosis., Methods: A retrospective analysis identified all patients with congenital scoliosis were retrospectively identified from the prospectively collected spine register from 2010 to 2022. Operative technique, perioperative laboratory results and imaging studies were extracted. The primary outcome was total blood loss including intraoperative, drain output and hidden blood loss., Results: Fifty-seven children (32 boys) with a mean age of 8.3 years underwent spinal osteotomy for congenital scoliosis. Posterolateral hemivertebrectomy was sufficient in 34 (59%) patients, while vertebral column resection (VCR) was required in 23 patients. Total bleeding averaged 792 (523) ml accounting for 42% of the estimated blood volume. Hidden blood loss accounted for 40% of total bleeding and 21% of estimated blood volume with a mean of 317 (256) ml. VCR was associated with greater intraoperative and total bleeding than hemivertebrectomies (p = 0.001 and 0.007, respectively). After adjusting for patient weight and fusion levels, hidden blood loss was larger in hemivertebrectomies (4.18 vs. 1.77 ml/kg/fused level, p = 0.049). In multivariable analysis, intraoperative blood loss was inversely correlated with preoperative erythrocyte levels. Younger age was associated with significantly greater drain, hidden and total blood loss., Conclusion: Hidden blood loss constitutes a significant portion (40%) of total bleeding in congenital scoliosis surgery. Younger age is a risk factor for bleeding and the hidden blood loss should be taken into consideration in their perioperative management., (© 2024. The Author(s).)

Objectives: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan., Methods: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant., Results: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before., Conclusions: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Increasing evidence demonstrates the advantages of an enhanced recovery after surgery (ERAS) protocol; however, few studies have evaluated ERAS in pediatric patients. This study aimed to evaluate the effect of ERAS in pediatric patients with congenital scoliosis. Seventy pediatric patients with congenital scoliosis underwent posterior hemivertebra resection and fusion with pedicle screws and were prospectively randomly assigned to the ERAS group ( n  = 35) and control group ( n  = 35). ERAS management comprised 15 elements including a shortened fasting time, optimized anesthesia protocol, and multimodal analgesia. The control group received traditional perioperative management. Clinical outcome was evaluated by hospital stay, surgery-related indicators, diet, pain scores, laboratory tests, and complications. The surgical outcome showed a similar correction rate in the ERAS group (84.0%) and control group (89.0%; P  = 0.471). The mean fasting time was significantly shorter in the ERAS group than in the control group. Compared with the control group, the ERAS group had significantly shorter mean times to postoperative hospital stay, first anal exhaust and defecation, significantly lower mean pain scores in the first 2 days postoperatively ( P  < 0.05), and a significantly lower mean interleukin-6 concentration on postoperative day 1 ( P  < 0.001). The incidence of complications was similar in the ERAS group and control group ( P  > 0.05). The ERAS protocol is effective and safe for pediatric patients with congenital spinal deformity and may significantly improve the treatment efficacy compared with traditional perioperative management methods. Levels of Evidence: III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2 , many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder., Competing Interests: Competing interests statement:J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron Genetics Center, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical genomic sequencing offered in the Baylor Genetics Laboratory (http://bmgl.com).

Background: The natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images., Methods: Congenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations., Results: Soft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change., Conclusions: Spinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae., (© 2024. The Author(s).)

Introduction: Although multimodal intraoperative neuromonitoring (IONM), which has high sensitivity and specificity, is typically performed during spinal deformity surgery, neurological status may deteriorate with delay after surgical maneuvers. Here, we report a rare case of delayed postoperative neurological deficit (DPND) that was not detected by IONM during posterior spinal fusion (PSF) for congenital scoliosis., Case Presentation: A 14-year-old male presented with congenital scoliosis associated with T3 and T10 hemivertebrae. Preoperative Cobb angle of proximal thoracic (PT) and main thoracic (MT) curves were 50° and 41°, respectively. PSF (T1-L1) without hemivertebrectomy was performed, and the curves were corrected to 31° and 21° in the PT and MT curves, respectively, without any abnormal findings in IONM, blood pressure, or hemoglobin level. However, postoperative neurological examination revealed complete loss of motor function. A revision surgery, release of the curve correction by removing the rods, was immediately performed and muscle strength completely recovered on the first postoperative day. Five days postoperatively, PSF was achieved with less curve correction (36° in the PT curve and 26° in the MT curve), without postoperative neurological deficits., Discussion: Possible mechanisms of DPND in our patient are spinal cord ischemia due to spinal cord traction caused by scoliosis correction and spinal cord kinking by the pedicle at the concave side. Understanding the possible mechanisms of intra- and postoperative neural injury is essential for appropriate intervention in each situation. Additionally, IONM should be continued to at least skin closure to detect DPND observed in our patient., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Compared to adult scoliosis, correcting scoliosis in children often presents greater challenges. This is attributed to two key factors. Firstly, it involves accounting for the growth potential of children. Secondly, the thinner pedicles in children can complicate screw insertion, particularly when dealing with existing deformities. The utilization of intraoperative navigation technology offers a modest improvement in the precision of screw placement but does come with the drawback of increased radiation exposure. The aim of this study is to investigate and assess the accuracy of manually inserting pedicle screws in the thoracic and lumbar spine to rectify deformities in children with early-onset congenital scoliosis., Methods: In this retrospective study, 26 hospitalized patients diagnosed with early-onset congenital scoliosis between December 2014 and December 2019 were selected. The cohort comprised 16 boys and 10 girls, aged between 2 and 10 years, with an average age of 4.68 ± 2.42 years. Pedicle screw fixation was applied in the segment spanning from T1 to L5. Pedicle screws were inserted manually, guided by the positioning of the C-arm and anatomical markers. The assessment of pedicle screw placement was based on the distance of penetration into the medial, lateral, or anterior bone cortex of the vertebral body, including the pedicle, categorized into three grades: Grade 1 (placement <2 mm), Grade 2 (placement between 2-4 mm), and Grade 3 (placement >4 mm). Grade 1 indicates accurate pedicle screw placement, while Grades 2 and 3 signify abnormal pedicle screw placement. Complications related to pedicle screw insertion were also recorded, both during and after the surgical procedure., Results: A total of 173 pedicle screws were inserted in this study, with an average of 6.65 screws per patient. Accurate screw placement was achieved in 143 cases (82.7%), while 30 pedicle screws were found to be abnormal. Among the abnormal screws, 24 were categorized as Grade 2 (13.9%), and 6 as Grade 3 (3.5%). Grade 2 abnormalities were distributed across 20 thoracic vertebrae and 4 lumbar vertebrae, while Grade 3 abnormalities affected 5 thoracic vertebrae and 1 lumbar vertebra. When comparing the lumbar and thoracic vertebral regions, a significant difference in the rate of abnormal screw placement was observed (χ 2 = 5.801, p < 0.05). The rate of abnormal screw placement was higher in the thoracic vertebral region with abnormal vertebral bodies than in the lumbar vertebral regions. Furthermore, a statistically significant difference in the rate of abnormal screw placement was found between the concave and convex sides (χ 2 = 23.047, p < 0.05). The concave side of the abnormal vertebral body had a higher rate of abnormal screw placement (55.6%, 15/27) compared to the convex side (20.1%, 7/34), and this difference was statistically significant ( p < 0.05). Throughout the intraoperative and postoperative follow-up period, spanning from 12 to 56 months, only one patient experienced issues with wound healing, and no complications related to pedicle screw placement occurred, such as hemopneumothorax, pedicle fracture, nerve root injury, aortic injury, screw loosening, pullout or breakage, or spinal cord injury., Conclusions: In children under 10 years of age with early-onset congenital scoliosis, the freehand placement of thoracic and lumbar pedicle screws demonstrates a high level of accuracy. Moreover, complications associated with pedicle screw insertion are infrequent following surgery. It is advisable to exercise caution when placing pedicle screws in thoracic vertebral bodies and morphologically abnormal vertebral bodies, with particular attention to the concave side when screw placement is required in these regions.

Background: To analyze the factors affecting the loss of correction effect in patients with congenital scoliosis after one stage posterior hemivertebra resection, orthosis, fusion and internal fixation., Methods: Thirty-nine patients with congenital scoliosis (CS) who underwent one-stage posterior hemivertebra resection, orthosis, fusion and internal fixation were retrospectively included in Hebei Children's Hospital General demographic information of patients was collected. Preoperative and postoperative imaging indicators were compared, Including cobb Angle of the main curvature of the spine, segmental Cobb Angle, compensatory cephalic curve, compensatory curve on the caudal side, segmental kyphosis, coronal balance, sagittal balance, thoracic kyphosis, lumbar lordosis, and apical vertebra translation. Correlation analysis is used to evaluate the factors affecting the loss of judgment and correction effect, and the correlation indicators are included in the multi-factor Logistics regression., Results: In terms of radiographic indicators in the coronal plane, compared to preoperative values, significant improvements were observed in postoperative Cobb Angle of main curve (8.00°±4.62° vs. 33.30°±9.86°), Segmental Cobb angle (11.87°±6.55° vs. 31.29°±10.03°), Compensatory cephalic curve (6.22°±6.33° vs. 14.75°±12.50°), Compensatory curve on the caudal side (5.58°±3.43° vs. 12.61°±8.72°), coronal balance (10.95 mm ± 8.65 mm vs. 13.52 mm ± 11.03 mm), and apical vertebra translation (5.96 mm ± 5.07 mm vs. 16.55 mm ± 8.39 mm) (all P < 0.05). In the sagittal plane, significant improvements were observed in Segmental kyposis Angle (7.60°±9.36° vs. 21.89°±14.62°, P < 0.05) as compared to preoperative values. At the last follow-up, Segmental kyphosis Angle (6.09°±9.75° vs. 21.89°±14.62°, P < 0.05), Thoracic kyphosis (26.57°±7.68° vs. 24.06°±10.49°, P < 0.05) and Lumbar lordosis (32.12°±13.15° vs. 27.84°±16.68°, P < 0.05) had statistical significance compared with the preoperative department. The correlation analysis showed that the correction effect of the main curve Cobb angle was correlated with fixed segment length (rs=-0.318, P = 0.048), postoperative segment Cobb angle (rs=-0.600, P < 0.001), preoperative apical vertebra translation (rs = 0.440, P = 0.005), and spinal cord malformation (rs=-0.437, P = 0.005). The correction effect of segmental kyphosis was correlated with age (rs = 0.388, P = 0.037). The results of the multivariate logistic regression analysis revealed that postoperative segmental Cobb angle > 10° (OR = 0.011, 95%CI:0.001-0.234, P = 0.004), associated spinal cord anomalies (OR = 24.369, 95%CI:1.057-561.793, P = 0.046), and preoperative apical translation > 10 mm (OR = 0.012, 95%CI:0.000-0.438, P = 0.016) were influential factors in the progression of the main curve Cobb angle., Conclusion: The one-stage posterior hemivertebra resection and short-segment corrective fusion with internal fixation are effective means to treat congenital scoliosis. However, attention should be paid to the loss of correction and curve progression during follow-up. Patients with spinal cord malformation and a large preoperative apical vertebra translation have a greater risk of losing the correction after surgery., (© 2023. The Author(s).)

Mutations in MYH3, the gene encoding the developmental myosin heavy chain-embryonic (MyHC-embryonic) skeletal muscle-specific contractile protein, cause several congenital contracture syndromes. Among these, recessive loss-of-function MYH3 mutations lead to spondylocarpotarsal synostosis (SCTS), characterized by vertebral fusions and scoliosis. We find that Myh3 germline knockout adult mice display SCTS phenotypes such as scoliosis and vertebral fusion, in addition to reduced body weight, muscle weight, myofiber size, and grip strength. Myh3 knockout mice also exhibit changes in muscle fiber type, altered satellite cell numbers and increased muscle fibrosis. A mass spectrometric analysis of embryonic skeletal muscle from Myh3 knockouts identified integrin signaling and cytoskeletal regulation as the most affected pathways. These pathways are closely connected to the mechanosensing Yes-associated protein (YAP) transcriptional regulator, which we found to be significantly activated in the skeletal muscle of Myh3 knockout mice. To test whether increased YAP signaling might underlie the musculoskeletal defects in Myh3 knockout mice, we treated these mice with CA3, a small molecule inhibitor of YAP signaling. This led to increased muscle fiber size, rescue of most muscle fiber type alterations, normalization of the satellite cell marker Pax7 levels, increased grip strength, reduced fibrosis, and decline in scoliosis in Myh3 knockout mice. Thus, increased YAP activation underlies the musculoskeletal defects seen in Myh3 knockout mice, indicating its significance as a key pathway to target in SCTS and other MYH3-related congenital syndromes., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Purpose: This study aimed to analyze the overall incidence of cardiac abnormalities in patients with congenital scoliosis and the possible influencing factors., Methods: PubMed, Embase, and Cochrane Library were searched for relevant studies. The quality of the studies was assessed independently by two authors using the methodological index for nonrandomized studies (MINORS) criteria. The following data were extracted from the included studies: bibliometric data, number of patients, number of patients with cardiac anomalies, gender, types of deformity, diagnostic method, type of cardiac anomaly, location, and other associated anomalies. The Review Manager 5.4 software was used to group and analyze all the extracted data., Results: This meta-analysis included nine studies and identified that 487 of 2,910 patients with congenital vertebral deformity had cardiac anomalies diagnosed by ultrasound (21.05%, 95% CI of 16.85-25.25%). The mitral valve prolapse was the most frequent cardiac anomaly (48.45%) followed by an unspecified valvular anomaly (39.81) and an atrial septal defect (29.98). A diagnosis of cardiac anomalies was highest in Europe (28.93%), followed by USA (27.21%) and China (15.33%). Females and formation defects were factors significantly associated with increased incidence of cardiac anomalies: 57.37%, 95% CI of 50.48-64.27% and 40.76%, 95% CI of 28.63-52.89%, respectively. Finally, 27.11% presented associated intramedullary anomalies., Conclusions: This meta-analysis revealed that the overall incidence of cardiac abnormalities detected in patients with congenital vertebral deformity was 22.56%. The incidence rate of cardiac anomalies was higher in females and those with formation defects. The study offers guidance for ultrasound practitioners to accurately identify and diagnose the most common cardiac anomalies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Congenital scoliosis(CS) is associated with multiple organs defect, and cardiac abnormalities have been reported commonly associated with CS. Hemivertebra is caused by the failure of vertebral formation, which is a major constitute of CS. Till now, few studies focus on the incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis. We aimed to analyze the cardiac defect in CS patients with or without hemivertebra, and further explore the incidence of cardiac defect between different types of hemivertebra., Methods: The ultrasonic cardiography (UCG) results of surgically treated congenital scoliosis (CS) patients between 2015 and 2018 were retrospectively analyzed. Patients were divided into hemivertebra group and non-hemivertebra group according to preoperative CT. Patients with hemivertebra was further divided into sub-group by single/multiple or fully/partially/mixed segmented hemivertebra. Demographic information, radiographic data and cardiac abnormalities were statistically compared between groups., Results: A total of 329 patients were analyzed, including 216 patients with hemivertebra and 113 patients without hemivertebra. UCG results were abnormal in 89 cases (27.1%), including 41 males(12.5%) and 48 females(14.6%). Hemivertebra group had comparable incidence of cardiac abnormalities with non-hemivertebra group (p = 0.517). No significant difference in the incidence of UCG abnormalities between single and multiple hemivertebra group (P = 0.246). Binary logistic regression analysis showed that female sex with multiple hemivertebra was a risk factor for abnormal UCG (P = 0.009, OR = 3.449). Cardiac abnormalities was comparable among fully, partially and mixed segmented hemivertebra group(P = 0.264). In abnormal UCG, 33 patients with hemivertebra had non-valvular abnormalities, and 48.5% (16/33) were septal defects. 28 patients had valvular abnormalities, most of them were mitral valve abnormalities, especially mitral valve redundancy, prolapse and insufficiency(82.1%, 23/28). No significant difference between the incidence of non-valvular and valvular abnormalities in patients with hemivertebra (P = 0.581)., Conclusions: The incidence of abnormal UCG results was approximately 28.2% in CS patients with hemivertebra. Female patients with multiple hemivertebra had a higher risk of UCG abnormalities. Mitral valve abnormalities were the most common abnormality of UCG found in CS patients with hemivertebra., Trial Registration: retrospectively registered., (© 2023. The Author(s).)

Background: The objective of this study was to evaluate the medium-term and long-term surgical outcomes of the 1-stage posterior-only lumbosacral hemivertebra resection with short-segment fusion in children., Methods: This retrospective chart review included 21 children with congenital scoliosis due to lumbosacral hemivertebra who received 1-stage posterior-only hemivertebra resection with short-segment fusion from 2012 to 2016 with at least 5 years of follow-up. Standing anteroposterior and lateral radiographs of the spine were compared preoperatively, postoperatively, and at last follow-up. Radiographic evaluation included measured changes in segmental scoliosis and lordosis, compensatory scoliosis, thoracic kyphosis, lumbar lordosis, trunk shift, and sagittal spinopelvic alignment., Results: There were 12 boys and 9 girls with a mean age of 6.5±3.2 years. The mean follow-up period was 6.7±1.3 years. The mean fusion level was 2.7±0.9 segments. The mean segmental scoliosis was 29±6 degrees preoperatively, 9±3 degrees (correction rate of 71%) postoperatively ( P <0.05), and 7±3 degrees (correction rate of 76%) at the latest follow-up. The compensatory curve of 26±12 degrees was spontaneously corrected to 14±8 degrees (correction rate of 47%) at last follow-up ( P <0.05). Trunk shift was significantly improved on both coronal (53%) and sagittal (56%) planes after surgery ( P 0.05) and stable at follow-up. The sagittal spinopelvic alignment was balanced in all cases. There were no neurological or infectious complications., Conclusions: It is safe and effective to perform 1-stage posterior-only lumbosacral hemivertebra resection with short-segment fusion, which can significantly correct the segmental scoliosis, prevent the compensatory curve progress and improve the trunk shift. This strategy also can save motion segments and avoid long lumbar fusion. Medium-term and long-term follow-up outcomes are satisfactory., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Several studies have elucidated the risk factors of intraoperative bleeding. However, the total blood loss (visible and hidden loss) and related risk factors were seldom reported. In this study, we aimed to identify predictors of massive blood loss in posterior hemivertebra resection for pediatric patients. Clinical records were retrospectively reviewed for 108 pediatric patients who underwent primary posterior hemivertebra resection and spinal fusion for congenital scoliosis from June 2017 to June 2019. Intraoperative blood loss was recorded and hidden blood loss was calculated by deducting the intraoperative loss from the total blood loss calculated using specific formula. Perioperative information was collected for multivariable linear regression analysis to determine the independent risk factors of the blood loss. The mean total blood loss was 575.0 ± 318.0 ml during the perioperative period, accounting for 42.1% of the estimated blood volume. The intraoperative and hidden loss were 337.6 ± 179.5 ml and 237.4 ± 204.8 ml, respectively, accounting for 58.7 and 41.3% of the total loss. Multivariable linear regression indicated that age, preoperative Cobb angle, operative time, and number of fused levels were independent risk factors of the total blood loss. Patients with operative time ≥145 minutes, fused levels ≥4, and preoperative Cobb angle ≥40° have an increased risk of massive blood loss. The perioperative blood loss of surgery for congenital scoliosis was considerable, with a high percentage of hidden blood loss. Patients with severe deformity, more fused levels, and longer operative time had higher risk of massive blood loss., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Congenital scoliosis (CS) represents the congenital defect disease, and poor segmental congenital scoliosis (PSCS) represents one of its types. Delayed intervention can result in disability and paralysis. In this study, we would identify the core biomarkers for PSCS progression through bioinformatics analysis combined with experimental verification., Methods: This work obtained the GSE11854 expression dataset associated with somite formation in the GEO database, which covers data of 13 samples. Thereafter, we utilized the edgeR of the R package to obtain DEGs in this dataset. Then, GO annotation, KEGG analyses, and DO annotation of DEGs were performed by "clusterProfiler" of the R package. This study performed LASSO regression for screening the optimal predicting factors for somite formation. Through RNA sequencing based on peripheral blood samples from healthy donors and PSCS cases, we obtained the RNA expression patterns and screen out DEGs using the R package DESeq2. The present work analyzed COL27A1 expression in PSCS patients by the RT-PCR assay., Results: A total of 443 genes from the GSE11854 dataset were identified as DEGs, which were involved in BP associated with DNA replication, CC associated with chromosomal region, and MF associated with ATPase activity. These DEGs were primarily enriched in the TGF- β signaling pathway and spinal deformity. Further, LASSO regression suggested that 9 DEGs acted as the signature markers for somite formation. We discovered altogether 162 DEGs in PSCS patients, which were involved in BP associated with cardiac myofibril assembly and MF associated with structural constituent of muscle. However, these 162 DEGs were not significantly correlated with any pathways. Finally, COL27A1 was identified as the only intersected gene between the best predictors for somite formation and PSCS-related DEGs, which was significantly downregulated in PSCS patients., Conclusion: This work sheds novel lights on DEGs related to the PSCS pathogenic mechanism, and COL27A1 is the possible therapeutic target for PSCS. Findings in this work may contribute to developing therapeutic strategies for PSCS., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2022 Zongshan Hu et al.)

Purpose: Hemivertebra is one of the common pathogenesis of congenital scoliosis. The timing of operation is undefined. Our study compared the surgical outcomes in children under age 10 years with scoliosis due to single nonincarcerated thoracolumbar hemivertebra according to the age at surgery., Methods: From January 2009 to August 2017, we retrospectively investigated 34 consecutive cases of congenital scoliosis treated by posterior hemivertebra resection and fusion with pedicle screw fixation. All cases were divided into two groups according to the age at surgery and followed-up for at least 2 years, group 1 (≤ 5 years old), and group 2 (5 to 10 years old)., Results: The mean Cobb angle of the main curve was improved from 48.58° to 15.53° (68.05%) in group 1, and from 43.73° to 11.33° (75.43%) in group 2. The segmental curve was improved from 44.16° to 11.53° (74.64%) in group 1, and the segmental curve was consistent with the main curve in group 2. The mean segmental kyphosis was improved from 27.50° to 8.42° (67.40%) in group 1, and from 29.00° to 5.00° (84.73%) in group 2. Five patients developed distal adding-on, and four patients were found proximal junctional kyphosis during the follow-up., Conclusion: Not all the deformities caused by single nonincarcerated thoracolumbar hemivertebra would progress greatly with the spinal growth. No significant statistical differences were found in the coronal and sagittal correction rate between the two groups. A limited delayed surgery after 5 years but before 10 years of age with close follow-up can achieve satisfied results., (© 2021. The Author(s).)

Congenital scoliosis (CS) is a lateral curvature of the spine resulting from congenital vertebral malformations (CVMs) and affects 0.5-1/1000 live births. The copy number variant (CNV) at chromosome 16p11.2 has been implicated in CVMs and recent studies identified a compound heterozygosity of 16p11.2 microdeletion and TBX6 variant/haplotype causing CS in multiple cohorts, which explains about 5-10% of the affected cases. Here, we studied the genetic etiology of CS by analyzing CNVs in a cohort of 67 patients with congenital hemivertebrae and 125 family controls. We employed both candidate gene and family-based approaches to filter CNVs called from whole exome sequencing data. This identified 12 CNVs in four scoliosis-associated genes ( TBX6 , NOTCH2 , DSCAM , and SNTG1 ) as well as eight recessive and 64 novel rare CNVs in 15 additional genes. Some candidates, such as DHX40 , NBPF20 , RASA2 , and MYSM1 , have been found to be associated with syndromes with scoliosis or implicated in bone/spine development. In particular, the MYSM1 mutant mouse showed spinal deformities. Our findings suggest that, in addition to the 16p11.2 microdeletion, other CNVs are potentially important in predisposing to CS.

FGFR1 encodes a transmembrane cytokine receptor, which is involved in the early development of the human embryo and plays an important role in gastrulation, organ specification and patterning of various tissues. Pathogenic FGFR1 variants have been associated with Kallmann syndrome and hypogonadotropic hypogonadism. In our congenital scoliosis (CS) patient series of 424 sporadic CS patients under the framework of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, we identified four unrelated patients harboring FGFR1 variants, including one frameshift and three missense variants. These variants were predicted to be deleterious by in silico prediction and conservation analysis. Signaling activities and expression levels of the mutated protein were evaluated in vitro and compared to that of the wild type (WT) FGFR1 . As a result, the overall protein expressions of c.2334dupC, c.2339T>C and c.1261A>G were reduced to 43.9%, 63.4% and 77.4%, respectively. By the reporter gene assay, we observed significantly reduced activity for c.2334dupC, c.2339T>C and c.1261A>G, indicating the diminished FGFR1 signaling pathway. In conclusion, FGFR1 variants identified in our patients led to only mild disruption to protein function, caused milder skeletal and cardiac phenotypes than those reported previously.

Background: Surgical treatment of early-onset scoliosis (EOS) with rib-based implants such as the vertical expandable prosthetic titanium rib (VEPTR) is associated with a high rate of complications including surgical site infection, skin breakdown, and implant migration. Many of these complications warrant the need for unplanned reoperations, increasing the burden on an already vulnerable patient population, and introducing the further risk of infection. To provide insight into the risks of early intervention, we investigate the relationship between initial device implantation before the age of 3 and the rate of unplanned reoperation., Methods: A retrospective review was performed of all patients at a single institution who had undergone VEPTR insertion for EOS with at least a 2-year follow-up from 2007 to 2016. Patients were stratified into the case-cohort (0 to 2 y of age) or the comparison cohort (3 to 10 y of age) based on age at the time of device implantation. Multivariate regression accounting for age and scoliosis etiology was performed to identify factors predictive of unplanned reoperation., Results: A total of 137 of 185 patients treated with VEPTR were identified with 76 (56%) undergoing at least 1 unplanned reoperation during the study time period. There were 68 and 69 patients in the age 0- to 2-year and 3- to 10-year cohorts, respectively. Patients aged 0 to 2 years underwent a higher number of total procedures compared with those aged 3 to 10 (13.1±6.5 vs. 10.6±4.8, P=0.032). A significant difference was found in the rate of unplanned reoperation between the 2 cohorts with 44 (65%) patients aged 0 to 2 and 32 (46%) patients aged 3 to 10 undergoing at least 1 unplanned reoperation (P=0.031). Binary logistic multivariate regression accounting for age and scoliosis etiology demonstrated that patients aged 0 to 2 had a significantly greater odds of undergoing an unplanned reoperation (odds ratio=3.050; 95% confidence interval: 1.285-7.241; P=0.011) compared with patients aged 3 to 10 years., Conclusion: Overall, EOS patients aged 0 to 2 at initial VEPTR implantation are up to 3 times higher risk of undergoing an unplanned reoperation compared with those aged 3 to 10., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Megaloblastic anemia or bone marrow changes could occur after prolonged nitrous oxide inhalation via vitamin B 12 inactivation related DNA synthesis impairment. Previous researches have studied hematological changes with nitrous oxide exposure, but only in adults or adolescents. Pre-school age children with active hematopoietic red bone marrow are more vulnerable to potential side effects of nitrous oxide and might experience growth impairment. The purpose of our study was to analyze red blood cell morphology changes under nitrous oxide anesthesia in pre-school age children., Methods: One hundred thirty-six children under 5 years old scheduled for hemivertebra resection were analyzed. According to fresh gas type in anesthesia records, 71 children who received nitrous oxide in oxygen during anesthesia maintenance were categorized into the nitrous oxide group and the other 65 who received air in oxygen were the air group. Complete blood counts in perioperative period were assessed for anemia, macrocytosis, microcytosis, anisocytosis, hyperchromatosis and hypochromatosis. The peak value and change percentage were calculated for mean corpuscular volume and red cell distribution width., Results: Forty-two children in the air group (64.6%) and 30 in the nitrous oxide group (42.3%) developed anemia (P = 0.009). None developed macrocytosis in both groups. Postoperative mean corpuscular volume peaked (mean [95% confidence interval]) at 83.7(82.9-84.4) fL, and 83.2(82.4-83.9) fL and postoperative red cell distribution width at 13.8% (13.4-14.2%), and 13.9% (13.6-14.2%) for the air group and the nitrous oxide group. Both the relative change of mean corpuscular volume (P = 0.810) and red cell distribution width (P = 0.456) were similar between the two groups., Conclusions: No megaloblastic red blood cell changes were observed with nitrous oxide exposure for 4 h in pre-school age children undergoing hemivertebra resection.

Abstract: A 6-year-old girl presented with complaints of absent horizontal eye movements since birth. There was also associated progressive scoliosis for past 1 year. Neuroimaging revealed split pons sign, butterfly-shaped medulla, and prominent inferior olivary nuclei. The presence of congenital horizontal gaze palsy, childhood onset progressive scoliosis, and abnormal neuroimaging findings confirmed the diagnosis of horizontal gaze palsy with progressive scoliosis. This case highlights the importance of neuroimaging in a child presenting with horizontal gaze palsy and scoliosis that helped for starting early rehabilitation of the child, prevention of permanent vision loss, and parental counseling for future pregnancies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Congenital scoliosis (CS) is a spinal deformity present at birth due to underlying congenital vertebral malformation (CVM) that occurs during embryonic development. Hemivertebrae is the most common anomaly that causes CS. Recently, compound heterozygosity in TBX6 has been identified in Northern Chinese, Japanese, and European CS patient cohorts, which explains about 7%-10% of the affected population. In this report, we recruited 67 CS patients characterized with hemivertebrae in the Southern Chinese population and investigated the TBX6 variant and risk haplotype. We found that two patients with hemivertebrae in the thoracic spine and one patient with hemivertebrae in the lumbar spine carry the previously defined pathogenic TBX6 compound heterozygous variants. In addition, whole exome sequencing of patients with CS and their family members identified a de novo missense mutation (c.G47T: p.R16L) in another member of the T-box family, TBXT. This rare mutation compromised the binding of TBXT to its target sequence, leading to reduced transcriptional activity, and exhibited dominant-negative effect on wild-type TBXT. Our findings further highlight the importance of T-box family genes in the development of congenital scoliosis., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: This study aimed to explore the clinical application of three-dimensional (3D) printing technology in the surgical treatment of congenital scoliosis caused by hemivertebrae., Methods: Twenty-four patients (11 in the 3D-printing group and 13 in the conventional group) with scoliosis secondary to a single hemivertebra were retrospectively reviewed. All patients underwent hemivertebrectomy and short-segment fixation. Virtual preoperative planning, operation simulation, and intraoperative application of 3D-printed patient-specific templates were performed in the 3D-printing group. Hemorrhage volume, operation time, transfusion, and complications were noted. Radiographic parameters were evaluated preoperatively, postoperatively, and at final follow-up., Results: All patients had different degrees of successfully corrected scoliosis. There was a similar correction of the Cobb angle postoperatively between the 2 groups. The operation time, blood loss, transfusion, time for the insertion of each screw, accuracy of screw placement, and complication rate in the 3D-printing group were significantly superior to those in the control group. No patient experienced major complications. No significant correction loss or instrument dysfunction was observed during follow-up., Conclusions: As a viable and effective auxiliary technology, 3D printing makes it possible for surgery to meet both surgeon-specific and patient-specific requirements. 3D-printed individualized templates allow surgery for the correction of congenital scoliosis to enter a new stage of personalized precision surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Arthrogryposis multiplex congenita (AMC) is a condition that describes neonates born with ≥2 distinct congenital contractures. Despite spinal deformity in 3% to 69% of patients, inadequate data exist on growth-friendly instrumentation (GFI) in AMC. Our study objectives were to describe current GFI trends in children with AMC and early-onset scoliosis (EOS) and to compare long-term outcomes with a matched idiopathic EOS (IEOS) cohort to determine whether spinal rigidity or extremity contractures influenced outcomes., Methods: Children with AMC and spinal deformity of ≥30° who were treated with GFI for ≥24 months were identified from a multicenter EOS database (1993 to 2017). Propensity scoring matched 35 patients with AMC to 112 patients with IEOS with regard to age, sex, construct, and curve. Multivariable linear mixed modeling compared changes in spinal deformity and the 24-item Early Onset Scoliosis Questionnaire (EOSQ-24) across cohorts. Cohort complications and reoperations were analyzed using multivariable Poisson regression., Results: Preoperatively, groups did not differ with regard to age (p = 0.87), sex (p = 0.96), construct (p = 0.62), rate of nonoperative treatment (p = 0.54), and major coronal curve magnitude (p = 0.96). After the index GFI, patients with AMC had reduced percentage of coronal correction (35% compared with 44%; p = 0.01), larger residual coronal curves (49° compared with 42°; p = 0.03), and comparable percentage of kyphosis correction (17% compared with 21%; p = 0.52). In GFI graduates (n = 81), final coronal curve magnitude (55° compared with 43°; p = 0.22) and final sagittal curve magnitude (47° compared with 47°; p = 0.45) were not significantly different at the latest follow-up after definitive surgery. The patients with AMC had reduced T1-S1 length (p < 0.001), comparable T1-S1 growth velocity (0.66 compared with 0.85 mm/month; p = 0.05), and poorer EOSQ-24 scores at the time of the latest follow-up (64 compared with 83 points; p < 0.001). After adjusting for ambulatory status and GFI duration, patients with AMC developed 51% more complications (incidence rate ratio, 1.51 [95% confidence interval (CI), 1.11 to 2.04]; p = 0.009) and 0.2 more complications/year (95% CI, 0.02 to 0.33 more; p = 0.03) compared with patients with IEOS., Conclusions: Patients with AMC and EOS experienced less initial deformity correction after the index surgical procedure, but final GFI curve magnitudes and total T1-S1 growth during active treatment were statistically and clinically comparable with IEOS. Nonambulatory patients with AMC with longer GFI treatment durations developed the most complications. Multidisciplinary perioperative management is necessary to optimize GFI and to improve quality of life in this complex population., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and “yes” to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work (http://links.lww.com/JBJS/G318)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Posterior hemivertebra resection and short-segment fusion with pedicle screws are an established treatment in congenital scoliosis, which require pediatric-specific instrumentation. The purpose of this study was to report the results of utilizing cervical lateral mass screws instead of pedicle screws in the treatment of congenital scoliosis in children younger than 5 years old., Methods: In an IRB-approved retrospective chart review study, patients <5 years old with congenital scoliosis who underwent posterior hemivertebra resection and fusion with lateral mass screws from 2013 to 2017 were included. Demographic information, pre- and post-operative radiographs, complications, and outcomes were extracted from the charts., Results: Twenty-three patients were included in the final analysis with a mean age of 40 months, of which 14 were female. Patients were followed for a mean of 51.3±13.2 months. The mean blood loss was 210ml, and patients were hospitalized for a mean of 4 days post-operatively. The correction rate of the main coronal curve, compensatory cranial curve, compensatory caudal curve, and segmental sagittal curve was 74.8%, 68%, 65.2%, and 68.9%, respectively. Three complications were observed: one intra-operative pedicle fracture, one case of implant failure, and one deep surgical-site infection, all of which were successfully managed., Conclusions: Our findings suggest that adult lateral mass screws can be used for transpedicular fixation of the thoracic and lumbar vertebrae in low-resource settings where pediatric-specific pedicle instruments are not readily available. The correction rate, outcomes, and complications are similar and comparable to pediatric-specific pedicle screws, in addition to being low-profile and less bulky compared to adult implants.

Background: Treatment of congenital hemivertebra is challenging and data on long-term follow-up (≥ 5 years) are lacking. This study evaluated the surgical outcomes of posterior thoracolumbar hemivertebra resection and short-segment fusion with pedicle screw fixation for treatment of congenital scoliosis with over 5-year follow-up., Methods: This study evaluated 27 consecutive patients with congenital scoliosis who underwent posterior thoracolumbar hemivertebra resection and short-segment fusion from January 2007 to January 2015. Segmental scoliosis, total main scoliosis, compensatory cranial curve, compensatory caudal curve, trunk shift, shoulder balance, segmental kyphosis, and sagittal balance were measured on radiographs. Radiographic outcomes and all intraoperative and postoperative complications were recorded., Results: The segmental main curve was 40.35° preoperatively, 11.94° postoperatively, and 13.24° at final follow-up, with an average correction of 65.9%. The total main curve was 43.39° preoperatively, 14.13° postoperatively, and 16.06° at final follow-up, with an average correction of 60.2%. The caudal and cranial compensatory curves were corrected from 15.78° and 13.21° to 3.57° and 6.83° postoperatively and 4.38° and 7.65° at final follow-up, with an average correction of 69.2% and 30.3%, respectively. The segmental kyphosis was corrected from 34.30° to 15.88° postoperatively and 15.12° at final follow-up, with an average correction of 61.9%. A significant correction (p < 0.001) in segmental scoliosis, total main curve, caudal compensatory curves and segmental kyphosis was observed from preoperative to the final follow-up. The correction in the compensatory cranial curve was significant between preoperative and postoperative and 2-year follow-up (p < 0.001), but a statistically significant difference was not observed between the preoperative and final follow-up (p > 0.001). There were two implant migrations, two postoperative curve progressions, five cases of proximal junctional kyphosis, and four cases of adding-on phenomena., Conclusion: Posterior thoracolumbar hemivertebra resection after short-segment fusion with pedicle screw fixation in congenital scoliosis is a safe and effective method for treatment and can achieve rigid fixation and deformity correction.

Abstract: The aim of the study was to determine if multiple intraspinal anomalies increase the risk of scoliosis correction compared to the normal intraspinal condition or 1 or 2 intraspinal anomalies in congenital scoliosis (CS) and whether correction for multiple intraspinal anomalies need to be performed with preliminary neurosurgical intervention before scoliosis correction.A total of 318 consecutive CS patients who underwent corrective surgery without preliminary neurosurgical intervention at a single institution from 2008 to 2016 were retrospectively reviewed, with a minimum of 2 years of follow-up. The patients were divided into 3 groups according to different intraspinal conditions. In the normal group (N group; n = 196), patients did not have intraspinal anomalies. In the abnormal group (A group; n = 93), patients had 1 or 2 intraspinal anomalies. In the multiple anomaly group (M group; n = 29), patients had 3 or more intraspinal anomalies including syringomyelia, split cord malformation [SCM], tethered cord, low conus, intraspinal mass, Chiari malformation or/and arachnoid cyst. The occurrence of complications as well as perioperative and radiographic data were analyzed.The incidence rate of multiple intraspinal anomalies in CS patients was 9.1% (29/318). No significant difference was observed in the perioperative outcomes or radiographic parameters at the final follow-up. There were no significant differences among the 3 groups in the total, major or neurological complication rates (all P > .05). Two patients (1 in the N group and 1 in the A group) experienced transient neurological complications, whereas no patient experienced permanent neurological deficits during surgery or follow-up.To our knowledge, the current study reported the largest cohort of intraspinal anomalies in patients with CS that has been reported in the literature. The results of our study demonstrated that patients with congenital scoliosis associated with intraspinal anomalies, even multiple intraspinal anomalies that coexist with more complex intraspinal pathologies, may safely and effectively achieve scoliosis correction without preliminary neurological intervention. More complex intraspinal pathologies do not seem to increase the risk of neurosurgical complications during corrective surgery., Competing Interests: Each author certifies that he or she, or a member of their immediate family, has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Congenital cervical scoliosis is rare, and there is a paucity of literature describing surgical outcomes. We report surgical outcomes in a 17-patient cohort with surgical correction for congenital cervical scoliosis and identify risk factors associated with complications., Methods: Data were retrospectively collected from a single-center cohort of 17 consecutive patients (9 boys, 8 girls) receiving surgical deformity correction for congenital cervical scoliosis. The mean age at surgery was 7.1±3.4 years with an average follow-up of 3.6±1.1 years., Results: There were 24 operations performed on 17 patients, and 4 complications (17%) were reported in the series, including one each of pressure ulcer, asystole, vertebral artery injury, and pseudarthrosis. The mean preoperative major curve angle was 36±20 degrees, which improved to 24±14 degrees (P=0.02). The mean operative time was 8±2 hours with a mean estimated blood loss of 298±690 mL. Halo-gravity traction was used in 5 patients and 6 cases were staged with anterior/posterior procedures., Conclusions: Congenital scoliosis of the cervical spine is a complex process. The spinal deformity of this nature can be managed successfully with carefully planned and executed surgical correction., Level of Evidence: Level IV-retrospective review., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height., Case Presentation: We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature., Conclusion: Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

Background: Previous studies have reported the progression of deformity in patients with adolescent idiopathic scoliosis after implant removal. However, for patients with congenital scoliosis, few studies have investigated the prognosis after implant removal., Methods: We observed 24 patients with congenital scoliosis, who underwent implant removal, for at least 3 years. Radiographic parameters and demographic data were compared to evaluate whether implant removal would lead to deformity progression., Results: Four of the 24 patients (16.7%) suffered correction loss and underwent revision surgery (RS). All correction losses occurred within 12 months of implant removal. The average curve of fixed segments (9.84° ± 7.22° to 16.42° ± 16.79°; P = 0.017) and kyphosis of fixed segments (10.46° ± 13.42° to 18.98° ± 25.99°; P = 0.03) increased significantly throughout the follow-up. After excluding patients who underwent RS, the changes in curve of fixed segments (9.10°-11.58°) and kyphosis of fixed segments (8.50°-9.24°) were all within the measurement error. The coronal and sagittal balance maintained during the follow-up. Through comparison, we thought that the younger age and lower Risser's grade with larger scoliosis might be risk factors for correction loss., Conclusions: Implant removal after fusion surgery for congenital scoliosis may present loss of correction and require RS, thus preserving implants is recommended. When removal of instrumentation is inevitable, parents and patients should be counseled for potential loss of correction and RS, and patients should be monitored for the progression of deformity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purpose of this study was to assess the surgical outcomes of posterior vertebral column resection (PVCR) with short-segment fusion for pediatric patients with congenital kyphoscoliosis (CKS). The medical records of 12 consecutive pediatric patients with CKS due to hemivertebrae located in thoracolumbar and lumbar area that had undergone PVCR and presented for follow-up at a minimum of 2 years were retrospectively reviewed. The mean follow-up period was 56.2 months, and the mean age at the surgery was 9.2 years. We evaluated radiographic parameters using plain radiographs, and evaluated segmental correction using computed tomography imaging. The mean values of the preoperative Cobb angle (cranial curve, main curve, and caudal curve) were 16.0°, 41.3°, and 25.0°, respectively. The main curve was reduced 5.4° after surgery and was maintained at 6.3° at the time of the most recent follow-up. The overall correction rate of main curve was 86.6%. Spontaneous correction rate in the cranial curve and caudal curve were calculated as 55.9 and 80.8%, respectively. The mean segmental scoliosis in the osteotomized segments and fused segments at preoperative/postoperative/final follow-up (FFU) were 40.8°/7.8°/9.2° and 34.3°/3.9°/5.1°, respectively. The mean segmental kyphosis in the osteotomized segments and fused segments at the preoperative/postoperative/FFU were 36.0°/3.8°/4.0° and 27.5°/-1.3°/0.7°, respectively. Our data indicate that PVCR with short-segment fusion for CKS can provide good correction in the main curve and spontaneous correction in the compensatory curves after a minimum 2-year follow-up. Further investigation over the long term is mandatory for pediatric patients.

Objective: This is the first systematic review and meta-analysis on the overall incidence of intraspinal abnormalities in patients with congenital scoliosis (CS) and potential influencing factors., Methods: We searched three large electronic databases (PubMed, EMBASE, and Cochrane Library) for potentially relevant studies. The quality of the included studies was assessed independently by two authors using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Data on the number of CS patients, number of CS patients with intraspinal abnormalities, sex of the patients, and CS types were extracted from the included studies. R software was used to pool and analyze all the extracted data., Results: This meta-analysis included 10 articles, and 671 of 1863 CS patients undergoing magnetic resonance imaging (MRI) examinations were identified to have intraspinal abnormalities. The overall incidence of intraspinal abnormalities in the patients with CS was 37% (95% CI, 29-45%). Diastematomyelia was the most common intraspinal abnormality and was detected in 45.60% of the patients with intraspinal abnormalities (306/671). The remaining intraspinal abnormalities included syringomyelia (273/671, 40.69%), tethered cord (190/671, 28.32%), low conus (58/671, 8.64%), intraspinal mass (39/671, 5.81%), Chiari malformation (32/671, 4.77%), fatty filum (27/671, 4.02%), spina bifida (occulta excluded) (17/671, 2.53%), tumor (17/671, 2.53%), cyst (12/671, 1.79%), syringomyelus (4/671, 0.60%), dural ectasia (1/671, 0.15%), and undiagnosed cord MRI hyperintensity (1/671, 0.15%). The patient's sex and CS type were not factors that affected the incidence of intraspinal abnormalities in CS patients (all P > 0.05)., Conclusions: This meta-analysis revealed that the overall incidence of intraspinal abnormalities detected by MRI in CS patients was 37%. Diastematomyelia was the most common intraspinal abnormality. The patient's sex and CS type were not factors that affected the incidence of intraspinal abnormalities in CS patients.

Background: The 6-minute walk test (6MWT) is used to assess the function of cardiopulmonary and neuromuscular conditions in adults and children. The primary research question was to determine the relationship between 6MWT distance and forced vital capacity (FVC) and the major curve among children with congenital scoliosis with rib anomalies., Methods: The authors recorded 6MWT distance in meters, FVC as a percentage of predicted normal value using arm span for height (FVC%), and Cobb angle in 20 children (13 girls; average age, 6.7±1.3 y) with congenital scoliosis before outpatient surgical treatment. The 6MWT uses a standardized protocol and measures distance traveled in 6 minutes on a flat surface. The authors then determined the correlation between these measures using linear regression analysis., Results: The Cobb angle of the major curvature was 55.4±20.5 degrees. The type of vertebral anomaly was mixed in 17 cases, formation failure in 2 cases, and segmentation failure in 1 case. The range of rib anomalies was 3.4±3.9 levels; 15 and 5 patients, respectively, had unilateral and bilateral rib anomalies. FVC and FVC% were 0.7±0.2 L and 60%±19%, respectively. The ratio of forced expiratory volume at 1 second to FVC (FEV1/FVC), which indicates obstructive lung disease, was normal at 93%±7%. The 6MWT distance was 386.3±59.4 m, which was ≤10% of the predicted distance for normal children. No child was able to walk the normal distance on the basis of published norms. 6MWT distance was significantly correlated with arm span (ρ=0.46, P=0.04) and major curve (ρ=-0.61, P=0.004), but not with FVC% (ρ=0.17, P=0.49)., Conclusions: The 6MWT distance is a feasible measure of function and is substantially reduced before surgery in children with thoracic congenital scoliosis with rib anomalies. The 6MWT distance was significantly correlated with a major curve but not with FVC%. 6MWT distance is not affected by moderate lung function impairment., Level of Evidence: Level IV-retrospective cohort study.

Background: Distal arthrogryposis (DA) is a group of rare Mendelian conditions that demonstrate heterogeneity with respect to genetics and phenotypes. Ten types of DAs, which collectively involve six genes, have been reported. Among them, the MYH3 gene causes several types of arthrogryposis conditions and therefore has a pivotal role in the skeletal and muscle development of the fetus. For this study, we recruited a five-generation Chinese family with members presenting DA features and phenotypic variability. Further clinical study characterized it as CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A)., Methods: Genomic DNA was extracted from eight family members, including one fetus. Whole-exome sequencing (WES) was then conducted on the proband's sample, followed by Sanger sequencing as validation for each of the participants. In silico analysis was performed. Western blotting (WB) detection and pathological staining were conducted on skeletal muscle tissue of the induced fetus after prenatal diagnosis., Results: A novel heterozygous pathogenic variant, namely NM&#95;002470.3: c.3044&#95;3047delinsTCAATTTGTT: p.E1015&#95;D1016delinsVNLF in the MYH3 gene, was identified and shown to be cosegregated with the condition in the subject family. This variant resulted in the replacement of amino-acid residues E1015 and D1016 by a string of VNLFs. The pregnancy was selectively terminated because the fetus was genetically affected. However, the WB and pathological results did not indicate a significant change in the norm., Conclusions: Our study expanded the variant spectrum of CPSFS1A, in addition to which it provided solid evidence for the appropriateness of genetic counseling and pregnancy management for the family. The results may also provide further insight into the molecular mechanism of MYH3., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Congenital scoliosis (CS) is a congenital disease resulting in abnormal vertebral development. Several studies have indicated that both genetic and environmental factors during pregnancy increase the risk of CS development. However, the exact mechanisms underlying CS pathogenesis remain unknown. To address this issue, both genetic (by whole‑exome sequencing) and epigenetic (by methylated DNA immunoprecipitation sequencing) maps from CS disease‑discordant monozygotic twins were generated in the present study. The differences in the presence of common and rare single nucleotide polymorphisms and in methylation patterns between the twins were investigated. The results indicated that rare mutations were more likely to underlie CS development compared with common mutations. Furthermore, differences in the allele‑specific methylation pattern in the supervillin (SVIL) gene between the twins were identified. It has been reported that SVIL exerts a number of functions associated with CS, indicating its role as a novel mechanism promoting CS pathogenesis.

Background: This study was designed to evaluate the treatment outcome of very young children with congenital scoliosis aged 3 years or under after surgery with a vertical expandable prosthetic titanium rib (VEPTR)-based distraction device., Methods: A retrospective study of 13 children undergoing implantation of a vertical expandable rib-based distraction device. From September 2007 to June 2018, 13 children (7 male and 6 female patients) with congenital scoliosis were followed after treatment with a VEPTR. The outcome parameters were complications, thoracic height, kyphosis, lordosis, and coronal major scoliosis curve. In addition, the American Society of Anaesthesiologists (ASA) score, assisted ventilation rating, and hemoglobin and body mass index were analyzed. Data were examined separately by 2 investigators., Results: The mean age at initial surgical treatment was 24.4±10.6 months, follow-up was 91.5±23.1 months. The mean number of surgical procedures per patient was 14±3.9 (total 182 operations). Apart from planned operations every 6 months, 5 unplanned operations (2.7%) were performed. The major scoliosis curve improved significantly from 55.2±21.9 degrees to 40.5±18.7 degrees, thoracic spine height T1-T12 significantly from 111±12 mm to 137±23 mm, T1-S1 height significantly from 211±13 mm to 252±36 mm and space available for the lung from 80.9%±11.3% to 84.4%±8.8% (preoperatively and at 5-y follow-up, respectively). Kyphosis increased significantly from 30±21.4 degrees to 42.6±23.5 degrees and lordosis from 32.4±20.9 degrees to 37.6±10.4 degrees. Hemoglobin levels were virtually unchanged. Weight increased from 10.6±2.8 kg to 20.2±5.0 kg at final follow-up, but body mass index decreased from 16.6±3.7 kg/m² to 15.7±2.9 kg/m²., Conclusions: The expandable rib-based distraction device is an effective method to treat severe congenital scoliosis in very young children. It can control the deformity and promotes spinal and thoracic growth., Level of Evidence: Level IV.

Objective: To investigate the efficacy and safety of preoperative halo-gravity traction and 1-stage posterior surgery for the treatment of scoliosis with intramedullary anomalies., Methods: A total of 11 patients with scoliosis with intramedullary anomalies were evaluated. All patients were treated with preoperative halo-gravity traction and 1-stage posterior surgery. The average age was 11.4 years (range, 7-21 years). All patients were followed-up for at least 2 years (mean, 3.5 years; range, 2-5 years). Their radiologic presentations and complications were reviewed., Results: The operating time was 7.9 hours, and the intraoperative bleeding amount was 1890 mL. Both the Cobb angle of scoliosis and kyphosis were significantly improved after halo-gravity traction and the operation (P < 0.05). Tethered cords were released, and intraspinal masses (neurofibromatosis and lipoma) were excised. Syringomyelia and split spinal cord malformations were left untreated. None of the patients experienced deterioration in their neurologic status after surgery. No severe complications, such as infection, cerebrospinal fluid leakage, failed internal fixation, or fractured pedicle screws or rods occurred after the operation. There was no deterioration of neurologic function, delayed infection, or pseudoarthrosis during the follow-up visits., Conclusions: Preoperative halo-gravity traction and 1-stage posterior surgery provided patients who had scoliosis and intramedullary anomalies an effective and safe treatment option with few complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Study Design: This was a multi-center retrospective cohort study included consecutive pediatric patients who were admitted to 8 institutions for the treatment of congenital spinal deformity from 1991 to 2012., Objective: The purpose of this study was to compare curve corrections and balances, reoperations, and complications at 2-year follow-up between those treated early vs. late. Although early intervention has been recommended, no empirical study has examined the optimal timing of short fusion among patients with congenital spinal deformity., Methods: Patients with congenital spinal deformity with formation failure undergoing vertebrectomy with short fusion (≤ 6 fusion segments) were categorized as early (surgery at ≤ 6 years) and late (7-18 years) fusion. Outcomes included coronal and sagittal curve corrections at immediate and 2-year evaluations; loss of curve correction from immediate to 2-year follow-up; coronal and sagittal balance at 2 years; and inter-operative, major and minor short-term postoperative, and long-term postoperative complications and reoperations., Results: Early fusion (N = 79) compared to late fusion (N = 96) was associated with greater percent curve correction at immediate (71% vs. 60%, p = 0.0046) and 2-year (63% vs. 52%, p = 0.0153) evaluations adjusting for surgeon experience and preoperative coronal balance. These associations were significant for males and those with 3-level fusions but not 4 to 6-level fusions. Early fusion compared with late fusion had more intraoperative (6% vs. 1%) and postoperative long-term complications (27% vs. 18%), as well as unplanned reoperations (13% vs. 9%). Early vs. late fusion had fewer short-term complications, both major (6% vs. 15%) and minor (6% vs. 15%)., Conclusions: Patients who underwent early treatment achieved larger major curve correction by 10% compared to patients with late treatment when assessed at 2-year postoperative evaluation. However, early fusion should be considered with careful attention to possible increased risk of reoperations., Level of Evidence: Level III.

Study Design: Case reports and review of the literature with a proposed management algorithm., Objectives: To report two cases of a potential vascular complication due to an incorrectly placed pedicle screw (PS) during spine deformity surgery. Relevant literature regarding the management of vascular complications is reviewed, and an evidence-based management algorithm is proposed. Aortic lesions represent a rare but potentially life-threatening complications with spine deformity and revision surgery, significantly increasing the risk. A management algorithm for an aortic lesion in the case of a malpositioned PS has not yet been published., Methods: Case 1: An 18-year-old female with proximal thoracic spinal non-instrumented fusion underwent a revision corrective procedure due to a progressive right-sided thoracolumbar compensatory curve. However, postoperative computed tomography (CT) performed to evaluate the position of the PS revealed malposition of the left T9 PS, which was abutting the descending aorta with CT angiography excluding the perforation of the aorta. Case 2: A 17-year-old male was scheduled for correction of Lenke 3-C-N adolescent idiopathic scoliosis. Postoperative routine evaluation with low-dose CT revealed a left T9 PS paravertebral malposition, and subsequent CTA demonstrated that the thread of the PS was in contact with the descending thoracic aorta and an unlikely hemodynamically significant vessel injury., Results: Successful removal of both malpositioned PS was performed. In the first case, a cardiovascular surgeon attended the operation if an urgent thoracotomy was needed, and in the second case, additional video-assisted thoracoscopic control of the aorta was performed during PS removal., Conclusions: Preoperative imaging in spinal surgery is essential to avoid major vascular and other complications when placing PS, especially in thoracic deformities. When a potential major vessel complication emerges, an interdisciplinary approach and an appropriate management algorithm are mandatory to make the best clinical decisions., Level of Evidence: 4.

Objective: To evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction for the treatment of severe and rigid congenital scoliosis (SRCS) associated with tethered spinal cord (TSC) and type II split cord malformation (SCM)., Methods: Thirteen patients with SRCS associated with TSC and type II SCM underwent posterior-only surgical correction with heavy halo-femoral traction. The preoperative mean coronal Cobb angle was 88.87° ± 12.15°; the mean flexibility was 15.28% ± 3.88%; and the mean angle of thoracic kyphosis and lumbar lordosis was 39.63° ± 18.47° and 56.99° ± 10.02°, respectively., Results: The mean duration of surgery was 320 ± 43.64 minutes and the mean blood loss was 1422.31 ± 457.59 mL. The mean follow-up period was 24.46 ± 7.53 months. After heavy halo-femoral traction, the mean coronal Cobb angle was reduced to 59.14° ± 8.75°. After posterior-only surgical correction, postoperative mean coronal Cobb angle was further reduced to 33.85° ± 8.77°. The postoperative mean correction rate was 62.46% ± 5.04%. The postoperative mean angle of thoracic kyphosis and lumbar lordosis was 29.31° ± 6.75° and 47.79° ± 3.68°, respectively. At the final follow-up, the corrective loss rate of Cobb angle was only 0.69%. There were no significant differences between final follow-up and preoperative modified Japanese Orthopaedic Association total scores. The Scoliosis Research Society-22 total score improved at the final follow-up evaluation compared with the preoperative total score., Conclusions: Without prophylactic neurosurgical intervention and spine-shortening osteotomy, posterior-only surgical correction with heavy halo-femoral traction could be safe and effective for the treatment of SRCS associated with TSC and type II SCM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Congenital scoliosis (CS) is a form of spinal curvature resulting from anomalous development of vertebrae. Recent studies demonstrated that circRNAs could serve as potential biomarkers of disease diagnosis. Genome-wide circRNAs expression in seven CS patients and three healthy controls was initially detected. Bioinformatics analysis was conducted to explore the potential pathological pathway of CS. Quantitative PCR (qPCR) was performed to validate the selected circRNAs in the replication cohort with 32 CS patients and 30 healthy controls. Logistic regression controlling for gender was conducted to compare the expression difference. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value. Twenty-two differentially expressed circRNAs were filtered from genome-wide circRNA sequencing. Seven circRNAs were validated by qPCR. Only hsa&#95;circ&#95;0006719 was confirmed to have a higher expression level in the CS group than the healthy control group (P = 0.036). Receiver operating characteristic curve also suggested that hsa&#95;circ&#95;0006719 had significant diagnostic value for CS (AUC = 0.739, P = 0.001). We described the first study of circRNAs in CS and validated hsa&#95;circ&#95;0006719 as a potential novel diagnostic biomarker of CS., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Study Design: Retrospective study., Objective: The aim of this study was to assess the presence of proximal junctional kyphosis (PJK) in our population of children with early-onset scoliosis (EOS) and to identify the predisposing factors for the development of PJK in the postoperative period after posterior spinal fusion (PSF). Few studies have been conducted to evaluate the incidence of proximal junction kyphosis (PJK) in children after early-onset scoliosis (EOS) after posterior spinal fusion (PSF)., Materials and Methods: Overall, 114 pediatric patients aged < 10 years who underwent surgery for scoliosis or kyphoscoliosis at a single center between 2013 and 2015 were evaluated. Forty-five patients submitted to PSF of five or more levels met the inclusion criteria. The sample included 12 female and 10 male patients. Mean age at surgery was 7 years and 8 months., Results: PJK was observed in 22 patients (48.9%). Overall, the mean proximal junctional angle at 12 and 36 months was 17.1° and 22°, respectively. The uppermost instrumented vertebra (UIV) with the highest PJK rate was T6-T7. The lowest instrumented vertebra (LIV) with the highest PJK rate was L2. Etiology was idiopathic in 4, neuromuscular in 11, congenital in 14, and syndromic in 16. According to underlying disorder, prevalence of PJK was 78% in those with a congenital, 50% in those with a syndromic, 12% in those with idiopathic, and 9% in those with a neuromuscular EOS. Surgical revision rate was 4% (one patient). Mean postoperative follow-up was of 3 years and 4 months (range 3-4 years and 1 month)., Conclusion: Congenital and syndromic etiology, but not age at PJK onset or sex of the patient, significantly affected the incidence rate of PJK. The UIV with the highest PJK rate was T6-T7 and the LIV with the highest PJK rate was L2. The patients had a low surgical revision rate., Level of Evidence: Level IV.