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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.)

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: 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.)

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: 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: 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.)

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: 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.

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: 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 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.)

Congenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish. We demonstrate that the scoliosis in dstyk mutants is related to the wavy and malformed notochord sheath formation and abnormal axial skeleton segmentation due to dysregulated biogenesis of notochord vacuoles and notochord function. Further studies show that DSTYK is located in late endosomal/lysosomal compartments and is involved in the lysosome biogenesis in mammalian cells. Dstyk knockdown inhibits notochord vacuole and lysosome biogenesis through mTORC1-dependent repression of TFEB nuclear translocation. Inhibition of mTORC1 activity can rescue the defect in notochord vacuole biogenesis and scoliosis in dstyk mutants. Together, our findings reveal a key role of DSTYK in notochord vacuole biogenesis, notochord morphogenesis and spine development through mTORC1/TFEB pathway.

Background: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity., Methods: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments., Results: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype., Conclusions: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Three-dimensional (3-D) printing offers the opportunity to create patient-specific guides for pedicle screw placement based on CT-generated models. This technology might allow for more-accurate placement of pedicle screws in patients with severe congenital scoliosis who have rotated vertebrae and small pedicles, but to our knowledge, this premise has not been tested., Questions/purposes: (1) Is the use of 3-D printing and pedicle guider technology as or more accurate than the use of the freehand technique for pedicle-screw placement in patients with severe congenital scoliosis? (2) Does surgical time differ with the use of these guiders? (3) Are complications less common in patients treated with this new approach to pedicle-screw placement?, Methods: A prospective controlled study was conducted of patients with severe congenital scoliosis (major curve ≥ 90°) from June 2016 to June 2018. During this period, we treated 93 patients with congenital scoliosis; 32 had severe scoliosis with a major curve ≥ 90°. The patients were divided into a pedicle guider group (n = 15) and a control group (n = 17) based on their willingness to use pedicle guider technology, which was considered a research technology. With the numbers available, there were no between-group differences in terms of age, sex, BMI, or parameters related to curve severity or flexibility, and all patients in both groups had severe curves. Preoperative and postoperative low-dose CT scans were performed in the two groups. In the pedicle guider group, custom software was used to design the pedicle guider, and a 3-D printer was used to print a physical spinal model and pedicle guiders. The pedicle guiders were tested on the surface of the physical spinal model before surgery to ensure proper fit, and then used to assist pedicle screw placement during surgery. A total of 244 screws were implanted with the help of 127 pedicle guiders (254 guiding tunnels) during surgery in the PG group. Five predesigned pedicle guiders were abandoned due to an unstable match, and the success rate of assisted screw placement using a pedicle guider was 96% (244 of 254). The freehand technique was used in the control group, which relied on anatomic localization to place pedicle screws. The accuracy of pedicle screw placement was evaluated with CT scans, which revealed whether screws had broken through the pedicle cortex. We compared the groups in terms of accuracy (defined as unanticipated breaches less than 2 mm), surgical time, time to place pedicle screws, and screw-related complications., Results: A higher proportion of the screws placed using pedicle guider technology were positioned accurately than were in the control group (93% [227 of 244] versus 78% [228 of 291]; odds ratio, 3.69 [95% CI, 2.09-6.50]; p<0.001). With pedicle guider use, operative time (296 ± 56 versus 360 ± 74; 95% CI, -111 to -17; p = 0.010), time to place all screws (92 ± 17 versus 118 ± 21; 95% CI, -39 to -12; p = 0.001), and mean time to place one screw (6 ± 1 versus 7 ± 1; 95% CI, -2 to 0; p = 0.011) decreased. One patient in the pedicle guider group and four in the control group experienced screw-related complications; the sample sizes and small number of complications precluded statistical comparisons., Conclusions: In this small, preliminary study, we showed that the accuracy of the surgical technique using spinal 3-D printing combined with pedicle guider technology in patients with severe congenital scoliosis was higher than the accuracy of the freehand technique. In addition, the technique using pedicle guider technology appeared to shorten operative time. If these findings are confirmed in a larger study, pedicle guider technology may be helpful for situations in which intraoperative CT or O-arm navigation is not available., Level of Evidence: Level II, therapeutic study.

Background: Although surgery prevents the progression of deformity and maintains the overall balance of the spine in congenital scoliosis (CS) patients, it is associated with a high risk of perioperative complications. Pulmonary complication is one of the most common complications. This retrospective study aimed to investigate the risk factors for pulmonary complications in CS patients after posterior spinal instrumentation and fusion., Methods: Analysis of consecutive patients who underwent posterior spinal instrumentation and fusion for congenital scoliosis was performed. Preoperative clinical data, intraoperative variables, and perioperative radiographic parameters were collected to analyze the risk factors for pulmonary complications. Patients were separated into groups with and without postoperative pulmonary complications. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of pulmonary complications., Results: Three hundred and twenty-three CS patients were included. Forty-five (13.9%) patients developed postoperative pulmonary complications, which included pleural effusion in 34 (75.6%) cases, pneumonia in 24 (53.3%) cases, pneumothorax in 3 (6.7%) cases, atelectasis in 4 (8.9%) cases, pulmonary edema in 2 (4.4%) cases, respiratory failure in 2 (4.4%) cases, and prolonged mechanical ventilation in 4 (8.9%) cases. The independent risk factors for development of pulmonary complications included age (Odds ratio (OR) = 1.088, P = 0.038), reoperation (OR = 5.150, P = 0.012), preoperative pulmonary disease (OR = 10.504, P = 0.004), correction rate (OR = 1.088, P = 0.001), middle thoracic screw-setting (OR = 12.690, P = 0.043), and thoracoplasty (OR = 5.802, P = 0.001). The area under the receiver operating characteristic (ROC) curve based on predicted probability of the logistic regression was 0.903., Conclusions: Age, reoperation, preoperative pulmonary disease, correction rate, middle thoracic screw-setting, and thoracoplasty were independent risk factors for pulmonary complications after posterior spinal instrumentation and fusion in CS patients.

Background: Patients who have a congenital spinal deformity with a tethered cord generally are treated with prophylactic intradural detethering before deformity correction. However, the detethering procedure carries substantial risk, and it is not clear whether deformity correction can be performed without detethering., Questions/purposes: To determine the (1) correction rate, (2) proportion of patients who experienced complications after surgery, and (3) neurological status after recovery from surgery in a group of patients with congenital spinal deformity and a tethered cord who were treated either with posterior spinal fusion only (PSF), pedicle-subtraction osteotomy (PSO), or a vertebral column resection (VCR), based on an algorithmic approach., Methods: Between 2006 and 2016, we treated 50 patients surgically for a congenital spinal deformity and a tethered cord. We defined a congenital spinal deformity as one that was caused by failure of vertebral segmentation, failure of vertebral formation, or both, and we made the diagnosis of a tethered cord based on a conus medullaris lower than L2 level, or a diameter of the filum terminale greater than 2 mm, as shown on magnetic resonance image. Of those, nine patients were lost to followup before the 2-year minimum, leaving 41 for analysis at a mean followup of 47 months (range, 24 to 92 months) in this single-institution retrospective study. The treatment algorithm involved one of three approaches: PSF, PSO, or VCR. A total of 15 patients underwent PSF; we used this approach for patients with moderate curves (Cobb angle < 80°) and intact neurological status both previously and during a bending and traction test. Eleven patients underwent PSO; we performed PSO when patients had neurological symptoms (in daily life or during the traction/bending test) and a magnitude of the curve less than 80°. Finally, 15 patients underwent VCR, which we used in patients with a magnitude of the curve more than 80° and/or flexibility less than 20%, with/without neurological symptoms. No patient in any group underwent intradural detethering. We report on the correction rate, defined as the ratio between the corrected magnitude and preoperative magnitude of a curve at a given postoperative time point (correction rate = 1- (Cobb angle at a given time point/preoperative Cobb angle) x 100%); complications, that is, postoperative/recurrent neurological symptoms, cerebrospinal fluid leakage, infection, blood loss > 5000 mL, as determined by chart review performed by an individual not directly involved in patient care; and a detailed neurological exam, including evaluations of sensory function, extremity muscle strength, pain, gait, physiological reflexes, and pathological signs, both before surgery and at most recent followup, as performed by the surgeon. All neurologically symptomatic patients were evaluated with a neurologic scoring system., Results: The overall mean ± SD correction rate in this series was 63% ± 14%. It was 70% ± 12% in the PSF group, 64% ± 17% in the PSO group, and 56% ± 12% in the VCR group. Seven patients in those three groups experienced major complications, including blood loss more than 5000 mL, temporary neurological symptoms, cerebrospinal fluid leakage, and infection. The most severe complications included one patient in the VCR group who had temporarily decreased strength in the lower limb, and one patient in the PSO group with temporary numbness in the lower limb. Finally, no patients in PSF group had postoperative neurological complications, and all patients with neurological symptoms in the PSO/VCR group improved to varying degrees. For neurologically symptomatic patients in PSO group (n = 6), the neurological score improved slightly, from 22.5 ± 1.9 preoperatively to 24.2 ± 0.8 at the most recent followup (p = 0.024) with a mean difference of 1.7. For neurologically symptomatic patients in VCR group (n = 10), the neurological score improved slightly from 23.1 ± 1.1 preoperatively to 24.2 ± 0.6 at most recent followup (p = 0.009) with a mean difference of 1.1., Conclusions: Congenital spinal deformity with a tethered cord may be treated without prophylactic intradural detethering. In the current series treated according to this treatment algorithm, good correction and neurological improvement were achieved, and few complications occurred. However, such a small series cannot prove the safety of this treatment; for that, larger, multicenter studies are necessary., Level of Evidence: Level IV, therapeutic study.

Purpose: To characterize clinically measurable endophenotypes, implicating the TBX6 compound inheritance model., Methods: Patients with congenital scoliosis (CS) from China(N = 345, cohort 1), Japan (N = 142, cohort 2), and the United States (N = 10, cohort 3) were studied. Clinically measurable endophenotypes were compared according to the TBX6 genotypes. A mouse model for Tbx6 compound inheritance (N = 52) was investigated by micro computed tomography (micro-CT). A clinical diagnostic algorithm (TACScore) was developed to assist in clinical recognition of TBX6-associated CS (TACS)., Results: In cohort 1, TACS patients (N = 33) were significantly younger at onset than the remaining CS patients (P = 0.02), presented with one or more hemivertebrae/butterfly vertebrae (P = 4.9 × 10 ‒8 ), and exhibited vertebral malformations involving the lower part of the spine (T8-S5, P = 4.4 × 10 ‒3 ); observations were confirmed in two replication cohorts. Simple rib anomalies were prevalent in TACS patients (P = 3.1 × 10 ‒7 ), while intraspinal anomalies were uncommon (P = 7.0 × 10 ‒7 ). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9 (P = 1.6 × 10 ‒15 ). A Tbx6 -/mh (mild-hypomorphic) mouse model supported that a gene dosage effect underlies the TACS phenotype., Conclusion: TACS is a clinically distinguishable entity with consistent clinically measurable endophenotypes. The type and distribution of vertebral column abnormalities in TBX6/Tbx6 compound inheritance implicate subtle perturbations in gene dosage as a cause of spine developmental birth defects responsible for about 10% of CS.

Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non-coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)-induced CS. Bioinformatics analysis and quantitative real-time PCR (qRT-PCR) indicated that SULT1C2A expression was down-regulated in VAD group, accompanied by increased expression of rno-miR-466c-5p but decreased expression of Foxo4 and somitogenesis-related genes such as Pax1, Nkx3-2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno-miR-466c-5p expression by direct binding, and rno-miR-466c-5p inhibited Foxo4 expression by binding to its 3' untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno-miR-466c-5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT-PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS. Thus, SULT1C2A may be a potential target for treating CS., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Spondylocarpotarsal synostosis syndrome, a rare syndromic skeletal disorder characterized by disrupted vertebral segmentation with vertebral fusion, scoliosis, short stature, and carpal/tarsal synostosis, has been associated with biallelic truncating mutations in the filamin B gene or monoallelic mutations in the myosin heavy chain 3 gene. We herein report the case of a patient with a typical phenotype of spondylocarpotarsal synostosis syndrome who had a homozygous frameshift mutation in the refilin A gene (RFLNA) [c.241delC, p.(Leu81Cysfs*111)], which encodes one of the filamin-binding proteins. Refilins, filamins, and myosins play critical roles in forming perinuclear actin caps, which change the nuclear morphology during cell migration and differentiation. The present study implies that RFLNA is an additional causative gene for spondylocarpotarsal synostosis syndrome in humans and a defect in forming actin bundles and perinuclear actin caps may be a critical mechanism for the development of spondylocarpotarsal synostosis syndrome.

This paper presented a special case and shortly described the congenital malformations of a child operated at the age of 2 years and 7 months. Medical literature does not mention the cases of double or triple congenital scoliosis. 54 patients were treated, out of whom, 39 were operated during the period of 2000 and 2012. This series presented 4 patients with double congenital scoliosis and 2 with triple congenital scoliosis. All these axial deviations were due to hemivertebrae with longitudinal imbalance of the spine, if these hemivertebrae were present on a distance of at least 5 normal vertebrae.

We report the surgical treatment course of a 4-year-old girl with congenital scoliosis, diastematomyelia and double adjacent hemivertebrae. She had a lumbar curve with an apparent pelvic obliquity. Simultaneous excision of double segmented sequential hemivertebra at the L3-L4 level and fusion with short-segment instrumentation was performed via a posterior approach. Intraoperative radiographs revealed satisfactory curve correction and 0° pelvic obliquity. Following the excision of double adjacent hemivertebrae, three adjacent nerve roots were placed in one intervertebral foramen bilaterally. Nevertheless, no neurological deficit was developed, and the patient was able to ambulate with a brace at day one. Pelvic balance and deformity correction were maintained with no implant failure at the fifth year follow-up. Excision of two ipsilateral adjacent hemivertebra and short-segment posterior fusion performed via posterior-only approach simultaneously is an effective, safe, and less invasive technique for the treatment of the described case., (Copyright © 2019 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

The presence of a pathology in the vertebral column of the early Permian mesosaurid specimen ZPAL R VII/1, being one of the oldest amniotic occurrences of congenital scoliosis caused by a hemivertebra, was recently recognized. Here we provide CT data to further characterize the phenomenon. The affected hemivertebra is wedged (incarcerated) between the preceding and succeeding vertebrae. The neural canal is misshapen but continuous and the number of dorsal ribs on each side of the specimen corresponds with the number of the vertebrae, documenting its congenital (homeobox-related) derivation., Competing Interests: The authors have declared that no competing interests exist.

Spondylocarpotarsal synostosis syndrome (SCT) is a rare group of skeletal dysplasias, characterized by disproportionate short stature with a short trunk, abnormal segmentation of the spine with vertebral fusion, scoliosis and lordosis, carpal and tarsal synostosis, and mild facial dysmorphisms. While the majority of the cases show autosomal recessive inheritance, only a few cases of vertical transmissions, with MYH3 mutations, have been reported. Here we report a case with typical SCT, carrying a novel heterozygous mutation in MYH3. This observation supports the hypothesis of a pathogenic link between autosomal dominant SCT and heterozygous mutations in MYH3. Of note, our case showed basilar invagination on brain magnetic resonance imaging at the age of 10 years. Basilar invagination could be a rare complication of both autosomal recessive and dominant SCT, indicating that prompt investigation are warranted for SCT patients.

Background: Congenital scoliosis (CS) may lead to more serious pulmonary complications compared with idiopathic scoliosis after spinal fusion surgery. However, little has been reported about postoperative pulmonary complication events in patients with CS after spinal fusion surgery., Objective: To investigate the incidence of and predictive factors of postoperative pulmonary complications following posterior spinal instrumentation and fusion surgery for the treatment of CS., Methods: We retrospectively reviewed the records of 174 patients with CS (128 females and 46 males, mean age 16.4 years) treated with posterior spinal instrumentation and fusion surgery between January 2012 and April 2017. We extracted demographic, medical history, and clinical data, and investigated the major predictive factors for postoperative pulmonary complications by logistic regression and receiver-operating characteristic curves analyses., Results: A total of 26 (14.9%) patients developed postoperative pulmonary complications, consisting of pleural effusion (10.9%), pneumonia (6.9%), pneumothorax (1.1%), atelectasis (2.3%), hypoxemia (6.3%), and respiratory failure (1.1%). Logistic regression analysis revealed that the predictive factors for postoperative pulmonary complications were age > 18.1 years (P = 0.039), a Cobb angle of > 77° (P = 0.011), operation time of > 430 min (P = 0.032), and blood transfusion volume > 1500 ml (P = 0.015)., Conclusions: Postoperative pulmonary complications are among the main complications following posterior spinal instrumentation and fusion surgery in patients with CS. Such patients aged >18.1 years, with Cobb angles > 77°, operation times > 430 min, and/or blood transfusion volume of > 1500 ml may be more likely to develop postoperative pulmonary complications., Competing Interests: The authors have declared that no competing interests exist.

Background: Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5-1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown., Methods: We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole-exome sequencing., Results: We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease-causing variants were identified in other patients, however. LFNG encodes a GlcNAc-transferase. The LFNG variants showed loss of their enzyme function., Conclusions: A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Rationale: Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect (VACTERL) association and Müllerian duct anomalies are rare conditions. We present a rare condition with the co-occurrence of the VACTERL association and Müllerian duct hypoplasia to characterize patients' clinical presentations, outcomes, and treatment., Patient Concerns: An 11-year-old girl presented to our hospital with severe lower abdominal pain, lower vaginal atresia with enlargement of the upper vagina and a bicornuate uterus with a Y-shaped uterine cavity filled with hematometra on pelvic magnetic resonance imaging. Her medical history included congenital anal atresia with a rectovestibular fistula, congenital right renal deficiency, congenital right thumb malformation, and scoliosis., Diagnoses: 1. Congenital genital tract malformations, a partial bicornuate uterus, and distal vaginal atresia (U3aC0V4); 2. VACTERL association (congenital anal atresia with rectovestibular fistula, scoliosis with hemi vertebra and butterfly vertebra, unilateral renal agenesis, and finger defect)., Interventions: Colpotomy, laparoscopic exploration, pelvic adhesiolysis, and hysteroscopy were performed., Outcomes: Two months after surgery, a pelvic examination showed an unobstructed vagina which was 10 cm long and 2 fingers wide, without adhesion or constriction., Lessons: Clinicians should have a high index of suspicion when evaluating patients with genital malformations associated with VACTERL. Early diagnosis of distal vaginal atresia with appropriate surgical intervention decreases long-term morbidity.

Background: The main treatment for congenital hemivertebra is posterior hemivertebrectomy with bilateral transpedicular fixation. To date, studies describing posterior unilateral fusion are few, especially in younger children. The modified method by posterior hemivertebrectomy combined with unilateral transpedicular instrumentation and fusion was described. The purpose was to present the clinical and radiological outcome of children less than 10 years treated for congenital scoliosis with posterior hemivertebrectomy and unilateral instrumented fusion., Methods: A study of 43 consecutive patients through Jan. 2006 to Mar. 2013 for hemivertebrae in children less than 10 years was performed. Patients undergoing hemivertebrectomy and posterior convex short-segment fusion, which had been followed up for at least 60 months, were included. Coronal main curve, kyphosis, T1-S1 height, fused vertebra height, and concave height were measured at preoperation, immediate postoperation, and final follow-up. The outcome and efficacy of the correction provided and growth of the non-fused concave side of the spine was investigated., Results: The average follow-up period was 73.88 ± 16.77 months. The mean Cobb angle of the coronal curve was improved from 46.1 to 8.1° (correction rate 82.4%). At final follow-up, there was 7.8% loss of correction. The average concave height, fusion segment height, and T1-S1 height were 60.1 ± 19.7 mm, 56.9 ± 22.9 mm, and 326.6 ± 64.5 mm in immediate postoperation, which improved to 73.1 ± 23.7 mm, 71.2 ± 22.0 mm, and 388.7 ± 78.9 mm at the last follow-up. These parameters were significantly different between the immediate postoperation and at final follow-up. The rate of reoperation was 9.3% (4/43), mainly in PJK and curve progression after surgery., Conclusions: Despite with some complications, posterior hemivertebrectomy and unilateral instrumented fusion are commendable procedures. We concluded that it is a simple, secure, reliable, less-invasive, and well-tolerated technique that can successfully resolve this kind of congenital scoliosis in children.

The location and/or type of variants in FLNB result in a spectrum of osteochondrodysplasias ranging from mild forms, like spondylocarpotarsal synostosis syndrome and Larsen syndrome, to severe perinatal lethal forms, such as atelosteogenesis I and III and Boomerang dysplasia. Spondylocarpotarsal synostosis syndrome is characterized by disproportionate short stature, vertebral anomalies and fusion of carpal and tarsal bones. Biallelic loss-of-function variants in FLNB are known to cause spondylocarpotarsal synostosis syndrome and 9 families and 9 pathogenic variants have been reported so far. We report clinical features of 10 additional patients from 7 families with spondylocarpotarsal synostosis syndrome due to 7 novel deleterious variants in FLNB, thus expanding the clinical and molecular repertoire of spondylocarpotarsal synostosis syndrome. Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal coalition) and molecular (truncating variants in FLNB) characteristics of this condition., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Spondylocarpotarsal synostosis syndrome (SCTS) is characterized by intervertebral fusions and fusion of the carpal and tarsal bones. Biallelic mutations in FLNB cause this condition in some families, whereas monoallelic variants in MYH3, encoding embryonic heavy chain myosin 3, have been implicated in dominantly inherited forms of the disorder. Here, five individuals without FLNB mutations from three families were hypothesized to be affected by recessive SCTS on account of sibling recurrence of the phenotype. Initial whole-exome sequencing (WES) showed that all five were heterozygous for one of two independent splice-site variants in MYH3. Despite evidence indicating that three of the five individuals shared two allelic haplotypes encompassing MYH3, no second variant could be located in the WES datasets. Subsequent genome sequencing of these three individuals demonstrated a variant altering a 5' UTR splice donor site (rs557849165 in MYH3) not represented by exome-capture platforms. When the cohort was expanded to 16 SCTS-affected individuals without FLNB mutations, nine had truncating mutations transmitted by unaffected parents, and six inherited the rs557849165 variant in trans, an observation at odds with the population allele frequency for this variant. The rs557849165 variant disrupts splicing in the 5' UTR but is still permissive of MYH3 translational initiation, albeit with reduced efficiency. Although some MYH3 variants cause dominant SCTS, these data indicate that others (notably truncating variants) do not, except in the context of compound heterozygosity for a second hypomorphic allele. These observations make genetic diagnosis challenging in the context of simplex presentations of the disorder., (Copyright © 2018 American Society of Human Genetics. All rights reserved.)

BACKGROUND The present study aimed to evaluate the pathogenicity of 5 [i]GDF3[/i] gene variations using functional and [i]in silico[/i] assessment approaches in a Chinese congenital scoliosis population. MATERIAL AND METHODS We selected 13 patients carrying 5 variants from a congenital scoliosis cohort. The PCR products of samples were verified by Sanger sequencing. The data and sequence alignment were analyzed using Chromas and ClustalW. SIFT and PolyPhen-2 were used to predict the functional effects of each missense and amino acid substitutions. SWISS-MODEL server and Swiss-PdbViewer were used to analyze conformational changes of GDF3 structure. DUET, UCSF Chimera, and Ligplot software were used to further explore the protein stability, side chains, and hydrophobic interaction changes, respectively. Luciferase reporter gene and Western blot assays were used to perform functional assessments for every variant from the molecular level. RESULTS Of the 13 patients, the S212L variant reoccurred in 9 patients. The rest of the patients carried 1 missense mutation each. The variants of R84L and R84C were predicted as probably damaging [i]loci[/i]. S212L, N215S, A251T were predicted as benign [i]loci[/i]. In functional assays, R84L, S212L, and A251T display inhibitory effects on functional assays. N251S mutation showed a negative effect in protein expression assays but not in luciferase reporter gene assays. The variant of R84C displayed no negative effects on 2 functional assays. CONCLUSIONS Our results suggest that the 4 of the 5 variants in [i]GDF3[/i] gene contribute different pathogenicity in congenital scoliosis, which may provide molecular evidence for clinical genetic testing.

Congenital scoliosis, a commonly seen disease occurring in children, can not only affect the growth, but also can uglify the individual which can severely affect the health and quality of life of children. To investigate the efficacy of posterior hemivertebra resection in combination with screw rod internal fixation in the treatment of congenital hemivertebra scoliosis, 115 patients were randomly divided into an observation group and a control group. Patients in the observation group were treated by posterior hemivertebra resection in combination with screw rod internal fixation, while patients in the control group were treated by posterior hemivertebra resection only. The surgical evaluation indicators, postoperative improvement of scoliosis and incidence of complications were recorded. The results demonstrated that the observation group had longer average operation time and less average blood loss compared to the control group, and the differences had statistical significance (P less than0.05); the correction efficacy of the observation group was superior to that of the control group (P less than 0.05); the incidence of postoperative complications in the two groups had no significant difference, but the incidence of correction loss of the observation group was much lower than that of the control group (P less than 0.05). In conclusion, posterior hemivertebra resection in combination with screw rod internal fixation is a highly efficient and safe treatment which can significantly relieve the clinical symptoms and cause few complications.

Congenital scoliosis (CS) is a three-dimensional deformity of the spine affecting quality of life. We have demonstrated TBX6 haploinsufficiency is the most important contributor to CS. However, the pathophysiology at the protein level remains unclear. Therefore, this study was to explore the differential proteome in serum of CS patients with TBX6 haploinsufficiency. Sera from nine CS patients with TBX6 haploinsufficiency and nine age- and gender-matched healthy controls were collected and analysed by isobaric tagged relative and absolute quantification (iTRAQ) labelling coupled with mass spectrometry (MS). In total, 277 proteins were detected and 20 proteins were designated as differentially expressed proteins, which were submitted to subsequent bioinformatics analysis. Gene Ontology classification analysis showed the biological process was primarily related to 'cellular process', molecular function 'structural molecule activity' and cellular component 'extracellular region'. IPA analysis revealed 'LXR/RXR activation' was the top pathway, which is a crucial pathway in lipid metabolism. Hierarchical clustering analysis generated two clusters. In summary, this study is the first proteomic research to delineate the total and differential serum proteins in TBX6 haploinsufficiency-caused CS. The proteins discovered in this experiment may serve as potential biomarkers for CS, and lipid metabolism might play important roles in the pathogenesis of CS., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Endosulfan is an organochlorine pesticide that is used extensively across the world to kill insects. Incidence of acute and chronic toxicity with endosulfan poisoning has been reported, and nearly 80 countries have banned its use. However, it is still being used in many low-income/middle-income countries. One of the most severe tragedies because of endosulfan poisoning has taken place in the Indian state of Kerala due to persistent aerial spraying of endosulfan. Even though there are reports of skeletal and other congenital abnormalities in humans and experimental animals following exposure to endosulfan, very few have been documented. We report two cases of congenital scoliosis in siblings living in a community affected by high levels of endosulfan in the environment. High index of suspicion is essential during the screening of school children exposed to endosulfan. Congenital scoliosis is a progressive deformity that leads to severe disability, unless detected and corrected at an early stage., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rationale: Situs inversus totalis is a rare anomaly disease in which the organs in the chest and abdomen are positioned in a mirror image reversal of normal positions. Although this has been confirmed to be associated with spinal abnormalities, reports about situs inversus totalis with congenital scoliosis remain limited., Patient Concerns: We present a 9-year-old girl having congenital scoliosis associated with situs inversus totalis., Diagnoses: She also had other associated anomalies: ventricular septal defect, mild restrictive ventilatory dysfunction, hydronephrosis, and syringomyelia. Her preoperative Cobb angle (T11-L3) was 78°., Interventions: She received single growing rods treatment and subsequent posterior spinal fusion correction surgery for her scoliosis., Outcomes: The coronal Cobb angle of the main curve was corrected to 20° postoperatively and no obvious loss of spinal corrective angle was identified 1 year after the correction surgery., Lessons: Growing rods technique could be a safe and effective alternative for the treatment of scoliosis associated with situs inversus totalis. In the correction of left-sided lumbar curve of this kind of patients, the risks of aorta impingements should not be neglected when placing pedicle screws on the concave sides., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vertebrae, ribs, and spinal cord are anatomically adjacent structures, and their close relationships are clinically important for planning better corrective surgical approach. The objective is to identify the radiographic characteristics in surgical patients with congenital scoliosis (CS) and coexisting split cord malformation (SCM)., Methods: A total of 266 patients with CS and SCM underwent surgical treatment at our hospital between May 2000 and December 2015 was retrospectively identified. The demographic distribution and radiographic data were collected to investigate the characteristics of spine curve, vertebral, rib, and intraspinal anomalies. According to Pang's classification, all patients were divided into two groups: type I group is defined as two hemicords, each within a separate dural tube separated by a bony or cartilaginous medial spur, while type II group is defined as two hemicords within a single dural tube separated by a nonrigid fibrous septum., Results: There were 104 patients (39.1%) in Type I group and 162 patients (60.9%) in Type II group. SCM was most commonly found in the lower thoracic and lumbar regions. The mean length of the septum in Type I SCM was significantly shorter than Type II SCM (2.7 vs. 5.2 segments). Patients in Type I group had a higher proportion of kyphotic deformity (22.1%). The vertebral deformities were simple in only 16.5% and multiple in 83.5% of 266 cases. Patients in Type I group presented higher prevalence of multiple (90.4%) and extensive (5.1 segments) malformation of vertebrae. In addition, hypertrophic lamina and bulbous spinous processes were more frequent in Type I group (29.7%), even developing into the "volcano-shape" deformities. Rib anomalies occurred in 62.8% of all patients and 46.1% of them were complex anomalies. The overall prevalence of other intraspinal anomalies was 42.9%. The most common coexisting intraspinal anomalies was syringomyelia (30.5%)., Conclusion: The current study, with the largest cohort to date, demonstrated that patients with CS and coexisting SCM presented high prevalence of multiple vertebral deformities, rib and intraspinal anomalies. The length of the split segment in Type I SCM was shorter than that in Type II SCM. Compared with Type II SCM, patients with Type I SCM presented with higher incidence of kyphotic deformity, more extensive and complicated vertebral anomalies, and more complex rib anomalies.

Lumbosacral hemivertebrae causes unique problems as early trunk decompensation and long compensatory curve above. There are only a few reports on it. This case series is a fair supplement in the literatures.To evaluate the clinical and radiological outcomes of lumbosacral hemivertebrae resection through 1-stage posterior approach.Between 2005 and 2014, a consecutive series of congenital scoliosis due to lumbosacral hemivertebrae underwent hemivertebrae excision through 1-stage posterior only approach. Demographic, operative, radiological, and quality of life data were reviewed.The mean lumbosacral curve was 29 ± 7° preoperatively, 10 ± 3° postoperatively, and 13 ± 5° at the final follow up. The final correction rate was 55 ± 9%. The gravity trunk shift was 11 ± 3 mm preoperatively, 37 ± 12 mm (range, 6-49 mm) postoperatively, 14 ± 9 mm at final follow up. The rib cage shift was 36 ± 12 mm preoperatively, 19 ± 5 mm postoperatively, and 15 ± 4 mm at the final follow up. The mean blood loss was 527 ± 125 mL and the mean surgery time was 336 ± 98 minutes. The mean follow up period was 41 ± 6 months. Two patients underwent transient neurological complications, 2 had wound bad healing, and 1 got wound infection. No pseudoarthrosis and instrumentation failure was observed.One-stage posterior hemivertebrae excision could gain reasonable outcome. It is crucial to completely resect the hemivertebrae and the Y-shaped disc. Bending the rod to appropriate lordosis is helpful to close the convex side. Early surgical intervene is a preferred choice to restore the trunk balance and avoid extensive fusion. The neurological complication rate is high. Convex radiculopathy is often caused by retraction, it could recover at follow up.