Spinal dysraphism in congenital scoliosis and kyphosis: a retrospective analysis in an Indian population.

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.

Delayed paraparesis after posterior spinal fusion for congenital scoliosis: a case report.

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.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model.

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.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

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.

Mitochondrial genes modulate the phenotypic expression of congenital scoliosis syndrome caused by mutations in the TBXT gene.

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.

Comparison and Evaluation of the Accuracy for Thoracic and Lumbar Pedicle Screw Fixation in Early-Onset Congenital Scoliosis Children.

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 (χ2 = 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 (χ2 = 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.

Hidden blood loss and bleeding characteristics in children with congenital scoliosis undergoing spinal osteotomies.

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.

A Study of Polish Family with Scoliosis and Limb Contractures Expands the MYH3 Disease Spectrum.

A disease associated with malfunction of the MYH3 gene is characterised by scoliosis, contractures of the V fingers, knees and elbows, dysplasia of the calf muscles, foot deformity and limb length asymmetry. The aim of this study was to identify the cause of musculoskeletal deformities in a three-generation Polish family by exome sequencing. The segregation of the newly described c.866A>C variant of the MYH3 gene in the family indicates an autosomal dominant model of inheritance. The detected MYH3 variant segregates the disease within the family. The presented results expand the MYH3 disease spectrum and emphasize the clinical diagnostic challenge in syndromes harbouring congenital spine defects and joint contractures.

Analysis of the factors affecting the loss of correction effect in patients with congenital scoliosis after one stage posterior hemivertebrae resection and orthosis fusion.

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.

The incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis.

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.

Musculoskeletal defects associated with myosin heavy chain-embryonic loss of function are mediated by the YAP signaling pathway.

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.

Incidence of cardiac anomalies in congenital vertebral deformity: systematic review and meta-analysis of 2910 patients.

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.

Medium-term and Long-term Follow-up Surgical Outcomes of the 1-stage Posterior-only Lumbosacral Hemivertebra Resection With Short-segment Fusion in Children.

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.

Overview of Gene Special Issue "Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis".

In this Special Issue of Genes entitled "Genetic Conditions Affecting the Skeleton: Congenital, Idiopathic Scoliosis and Arthrogryposis", evidence is presented which suggests that congenital, idiopathic scoliosis, and arthrogryposis share similar overlapping, but also distinct etiopathogenic mechanisms, including connective tissue and neuromuscular mechanisms [...].

Predictors of perioperative blood loss in primary posterior hemivertebra resection for pediatric patients with congenital scoliosis.

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.

Bi-allelic MYH3 loss-of-function variants cause a lethal form of contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B.

Arthrogryposis is a consequence of reduced fetal movements and arises due to environmental factors or underlying genetic defects, with extensive genetic heterogeneity. In many instances, the genes responsible are involved in neuromuscular function. Missense variants in the gene encoding embryonic myosin heavy chain (MYH3) usually cause distal arthrogryposis. Recently, mono-allelic or bi-allelic MYH3 variants have been associated with contractures, pterygia, and spondylocarpotarsal fusion syndrome 1 (CPSFS1A and CPSFS1B). Here we describe three fetuses presenting in the second trimester with a lethal form of arthrogryposis and pterygia and harbouring bi-allelic variants in MYH3. One proband was compound heterozygous for a missense change and an extended splice site variant, a second proband had a homozygous frameshift variant, and a third proband was homozygous for a nonsense variant. Minigene assays performed on the first fetus showed that the missense and extended splice site variants resulted in aberrant splicing, likely resulting in near complete loss of full-length MYH3 transcript. This study shows that loss of MYH3 is associated with a lethal arthrogryposis phenotype and highlights the utility of minigene assays to assess splicing.

Bioinformatics Analysis and Experimental Verification Identify Downregulation of COL27A1 in Poor Segmental Congenital Scoliosis.

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-ß 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.

Surgical outcomes in children under 10 years old in the treatment of congenital scoliosis due to single nonincarcerated thoracolumbar hemivertebra: according to the age at surgery.

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.

Novel FGFR1 Variants Are Associated with Congenital Scoliosis.

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.

Identification of Copy Number Variants in a Southern Chinese Cohort of Patients with Congenital Scoliosis.

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.