Gender-Specific Risk Factors for Asymmetric Bone Density in Adult Degenerative Lumbar Scoliosis: A Retrospective Cohort Analysis.

BACKGROUND This study aimed to evaluate the performance of Hounsfield Unit (HU) value on the vertebral bone mineral density associated with adult degenerative lumbar scoliosis (ADLS) and to compare the HU and coronal height changes of the lumbar spine on the concave and convex sides. The secondary aim was to investigate the risk factors for increased asymmetric ratio of HU (ARH) by concave-to-convex. MATERIAL AND METHODS A total of 74 patients aged ≥50 years were retrospectively reviewed. The height and the HU values of the region of interest were measured and compared. Multiple linear regression and gender-stratified analyses were performed to explore risk factors. Restricted cubic spline (RCS) was used to visually assess the dose-effect relationship between the Cobb angle and ARH. RESULTS The heights on the concave sides were significantly lower while HU values were significantly higher than that of the convex side. Cobb angle (95% CI: 0.001 to 0.009, P=0.034) was positively correlated with the increased ARH, while apex orientation to the right (95% CI: -0.152 to -0.013, P=0.022) was negatively associated. Gender-stratified analyses showed age and apex vertebrae location are 2 additional risk factors in male patients but not in female patients. Cobb angle was identified by RCS as a risk factor both in males and females and the inflection points were 15 and 17.5, respectively. CONCLUSIONS HU values on the concave side are significantly higher than on the convex side, showing the asymmetrical bone mass distribution of ADLS patients. Several gender-related risk factors for increased ARH have been identified.

Impact of Wheelchair Seating Systems on Scoliosis Progression for Children With Neurologic and Neuromuscular Disorders: A Retrospective Study of Custom-Contoured Wheelchair Seating and Modular Wheelchair Seating.

OBJECTIVES: To retrospectively evaluate the comparative effect of 2 wheelchair seating systems, Custom-Contoured Wheelchair Seating (CCS) and Modular Wheelchair Seating (MWS), on scoliosis progression in children with neuromuscular and neurologic disorders and to determine any predictors for scoliosis progression. DESIGN: Longitudinal, retrospective cohort study. SETTING: A national health service regional posture and mobility service. PARTICIPANTS: Nonambulant pediatric wheelchair users with neuromuscular and neurologic disorders (N=75; 36 men, 39 women; mean age at seating intervention, 10.50±3.97y) issued CCS and MWS by the South Wales Posture and Mobility Service from 2012-2022. INTERVENTIONS: Two specialized wheelchair seating systems, CCS and MWS. MAIN OUTCOME MEASURES: A generalized least squares model was used to estimate the effect of seat type on Cobb angle over time. RESULTS: Of the 75 participants enrolled, 51% had cerebral palsy. Fifty were issued CCS and 25 were issued MWS. Baseline Cobb angle was 32.9±18.9° for the MWS group and 48.0±31.0° for the CCS group. The generalized least squares model demonstrated that time since seating intervention (χ2=122, P<.0001), seating type (χ2=52.5, P<.0001), and baseline scoliosis severity (χ2=41.6, P<.0001) were predictive of scoliosis progression. Condition was not a strong predictor (χ2=9.96, P =.0069), and sex (χ2=5.67, P=.13) and age at intervention (χ2=4.47, P=.35) were not predictive. Estimated contrasts of medical condition with seat type over time demonstrated smaller differences between MWS and CCS over time. Predicted scoliosis velocity was found to attenuate with use of CCS over time compared with MWS, although scoliosis deteriorated regardless of intervention. CONCLUSIONS: Our findings showed pediatric wheelchair users with neurologic and neuromuscular disorders prescribed CCS showed greater mitigation of scoliosis progression over time compared with those issued MWS.

Elevated periodic limb movement index is associated with hypoxemia in children with early onset scoliosis.

PURPOSE: Patients with early onset scoliosis are at high risk of sleep disordered breathing, sleep disruption, and adverse consequences of poor sleep. In this study, we aim to assess the prevalence of periodic limb movements of sleep in a cohort of children with early onset scoliosis and identify factors that correlate with the presence of periodic limb movements. METHODS: This is a retrospective chart review of 40 patients with EOS (ages 1-17 years) who underwent a PSG from 2003 through 2019. Data collected included age, sex, and polysomnography parameters. Descriptive statistics were used: independent T test and Pearson correlation. RESULTS: The average age was 9.6 years (SD 5.2); 22 were female. Eleven patients (27.5%) had elevated periodic limb movement index (PLMI) (≥ 5). Those with PLMI ≥ 5 had arousal index of 15.4 (SD 7.2) and those with normal PLMI having an arousal index of 9.4 (SD 4.9); this reached statistical significance (p < 0.05). Those with elevated PLMI spent 4.9 (SD 8.3) minutes with saturations below 88%, while those with normal PLMI spent 1.0 (SD 1.8); this was statistically significant. There was a moderate positive correlation between arousal index, hypoxemia, and PLMI. CONCLUSION: The study suggests that children with early onset scoliosis have higher frequency of periodic limb movements during sleep, and these may be correlated with increased arousal and with hypoxemia.

Do middle-aged patients with onset of idiopathic scoliosis before the age of 10 years who have reduced pulmonary function have a risk for rapid decline - a comparative study.

BACK GROUND: Knowledge concerning pulmonary function in adult patients with onset of idiopathic scoliosis before age 10 is sparse. A long-term follow-up (FU, mean 26 years, > 12 years after treatment) of pulmonary function (PF) in patients treated with brace or surgery due to idiopathic scoliosis with onset before the age of 10 was earlier performed. To evaluate whether a more severe reduction in pulmonary function leads to more rapid deterioration within a four-year period, this study was performed. METHODS: Twenty patients with the most reduced pulmonary function and 19 out of those with normal PF found at the long-term FU were reexamined 4 years later to evaluate further changes in pulmonary function. Patients underwent spirometry and arterial blood gas analysis and answered pulmonary symptom questionnaires. RESULTS: 70% of the reduced pulmonary function group had undergone surgery vs. 26% of the normal group. The mean age (47 vs. 43 years) at this FU and curve size (37° vs. 35°) at the 26-year FU were similar. The decline in forced vital capacity (FVC) % of predicted was similar in both groups over the four-year period, from 67 to 65% in the reduced PF group vs. 96 to 94% in the normal PF group. The total lung capacity (TLC) % of predicted did not change over time in either group. No patient reported worsening dyspnea symptoms. Only one patient in the reduced PF group showed low arterial oxygen tension, 8.4 kPa, not signifying respiratory insufficiency. CONCLUSION: The age-related decline in FVC and TLC % of predicted did not differ between those with reduced and those with normal pulmonary function at the 26-year follow-up. Thus, these data do not infer increased rate of decline in the most deteriorated patients.

On growth and scoliosis.

PURPOSE: To describe the physiology of spinal growth in patients with adolescent idiopathic scoliosis (AIS). METHODS: Narrative review of the literature with a focus on mechanisms of growth. RESULTS: In his landmark publication On Growth and Form, D'Arcy Thompson wrote that the anatomy of an organism reflects the forces it is subjected to. This means that mechanical forces underlie the shape of tissues, organs and organisms, whether healthy or diseased. AIS is called idiopathic because the underlying cause of the deformation is unknown, although many factors are  associated. Eventually, however, any deformity is due to mechanical forces. It has long been shown that the typical curvature and rotation of the scoliotic spine could result from vertebrae and intervertebral discs growing faster than the ligaments attached to them. This raises the question why in AIS the ligaments do not keep up with the speed of spinal growth. The spine of an AIS patient deviates from healthy spines in various ways. Growth is later but faster, resulting in higher vertebrae and intervertebral discs. Vertebral bone density is lower, which suggests  less spinal compression. This also preserves the notochordal cells and the swelling pressure in the nucleus pulposus. Less spinal compression is due to limited muscular activity, and low muscle mass indeed underlies the lower body mass index (BMI) in AIS patients. Thus, AIS spines grow faster because there is less spinal compression that counteracts the force of growth (Hueter-Volkmann Law). Ligaments consist of collagen fibres that grow by tension, fibrillar sliding and the remodelling of cross-links. Growth and remodelling are enhanced by dynamic loading and by hormones like estrogen. However, they are opposed by static loading. CONCLUSION: Increased spinal elongation and reduced ligamental growth result in differential strain and a vicious circle of scoliotic deformation. Recognising the physical and biological cues that contribute to differential growth  allows earlier diagnosis of AIS and prevention in children at risk.

Biomechanical study of spinal cord and nerve root in idiopathic scoliosis: based on finite element analysis.

BACKGROUND: Current research lacks comprehensive investigation into the biomechanical changes in the spinal cord and nerve roots during scoliosis correction. This study employs finite element analysis to extensively explore these biomechanical variations across different Cobb angles, providing valuable insights for clinical treatment. METHODS: A personalized finite element model, incorporating vertebrae, ligaments, spinal cord, and nerve roots, was constructed using engineering software. Forces and displacements were applied to achieve Cobb angle improvements, designating T1/2-T4/5 as the upper segment, T5/6-T8/9 as the middle segment, and T9/10-L1/2 as the lower segment. Simulations under traction, pushing, and traction + torsion conditions were conducted, and biomechanical changes in each spinal cord segment and nerve roots were analyzed. RESULTS: Throughout the scoliosis correction process, the middle spinal cord segment consistently exhibited a risk of injury under various conditions and displacements. The lower spinal cord segment showed no significant injury changes under traction + torsion conditions. In the early correction phase, the upper spinal cord segment demonstrated a risk of injury under all conditions, and the lower spinal cord segment presented a risk of injury under pushing conditions. Traction conditions posed a risk of nerve injury on both sides in the middle and lower segments. Under pushing conditions, there was a risk of nerve injury on both sides in all segments. Traction + torsion conditions implicated a risk of injury to the right nerves in the upper segment, both sides in the middle segment, and the left side in the lower segment. In the later correction stage, there was a risk of injury to the upper spinal cord segment under traction + torsion conditions, the left nerves in the middle segment under traction conditions, and the right nerves in the upper segment under pushing conditions. CONCLUSION: When the correction rate reaches 61-68%, particular attention should be given to the upper-mid spinal cord. Pushing conditions also warrant attention to the lower spinal cord and the nerve roots on both sides of the main thoracic curve. Traction conditions require attention to nerve roots bilaterally in the middle and lower segments, while traction combined with torsion conditions necessitate focus on the right-side nerve roots in the upper segment, both sides in the middle segment, and the left-side nerve roots in the lower segment.

No effects of four weeks of combined brace and Schroth therapy in moderate adolescent idiopathic scoliosis on plantar pressure distribution.

BACKGROUND: Positive effects of brace treatments in adolescent idiopathic scoliosis patients on gait were proven. AIM: Therefore, this study examined whether the influence of brace therapy in combination with Schroth therapy influencing the plantar pressure distribution, pre and post intensive rehabilitative inpatient treatment. DESIGN: Prospective cohort study, longitudinal. SETTING: Scoliosis rehabilitation clinic "Asklepios Katharina-Schroth-Klinik" (Bad Sobernheim, Germany). POPULATION: Twenty (14f/6m) patients (12-16 years) had a medically diagnosed moderate idiopathic scoliosis (Cobb angle 20-50°, Median 30°) and an indication for combined brace and Schroth therapy with an inpatient stay (4 weeks) at the Asklepios Katharina Schroth Clinic (Germany). METHODS: At the beginning (T1) and at the end of the stay (T2), the plantar pressure distribution with (A) and without wearing a brace (B) was recorded (walking distance 10 m). RESULTS: No significant differences between the left and right foot were found at baseline (T1). The T1 - T2 comparison of one foot revealed significant differences (p ≤ 0.05 - 0.001, respectively) for (A): mean pressure right midfoot, loaded area total left foot, left midfoot, left inner ball of foot, right midfoot, impulse total right foot, right midfoot and for (B): mean pressure right midfoot, right outer ball of foot, loaded area total right foot, right heel, right midfoot, impulse right heel, right midfoot, right outer ball of foot. CONCLUSIONS: A combined brace and Schroth therapy maintains the initial symmetrical plantar pressure distribution over the duration of four weeks since the significant differences fall within the range of measurement error. CLINICAL REHABILITATION IMPACT: The insole measuring system can be used to objectively support therapeutic gait training as part of rehabilitation and to assess insole fitting based on foot shape. Due to its convenient handling and rapid data acquisition, it may be a suitable method for interim or follow-up diagnostics in the treatment of idiopathic scoliosis.

Optimization of traction parameters for lumbar scoliosis.

BACKGROUND: Scoliosis is a high incidence disease that endangers the physical and mental health of adolescents. Traction therapy, as a conservative treatment plan, is helpful to improve the recovery speed of patients by studying the influence of different traction factors on the therapeutic effect. METHODS: Based on the thin layer CT data of the lumbar spine of a 16-year-old patient with scoliosis, Mimics21.0 was used to extract the 3D digital model, and Geomagic Wrap2021 was used to perform the smooth surface. After that, SolidWorks was used to manually construct the structures, such as the intervertebral disc, and Ansys17.0 was used to add constraints, ligaments, and other features. Three-factor ANOVA was carried out after an orthogonal experiment that considered traction mode, traction angle, and traction force was finished. RESULTS: ① A three-dimensional biomechanical model of lumbar scoliosis was created. ② The model's correctness was confirmed by comparing it to the corpse and other finite element models, as well as by verifying it under a range of working settings. ③ Traction force (P = 0.000), traction angle (P = 0.000), the interaction between traction force and traction angle (P = 0.000), and the interaction between traction mode and traction angle (P = 0.045) were all significant. ④ The interaction between traction force and traction angle has the most significant effect on Cobb, and traction with a certain angle is better than traditional axial traction. ⑤ Traction mode is not significant, but the interaction between traction mode and traction angle is significant. CONCLUSIONS: A certain angle of traction can aid in improving outcomes and the traction force can be suitably decreased in the clinical formulation of the traction plan. The uniformity of correcting effect is more favorable when higher fixation techniques like positive suspension or traction bed traction are used, as opposed to overhanging traction.

Rare Sagittal Compensatory Balance in Neuromuscular Scoliosis Complicated by Hydrocephalus: A Case Report.

Objective: This case report aims to present a rare case of thoracic lordosis and lumbar kyphosis and describe the posterior instrumented scoliosis correction performed. Case presentation: A 59-year-old female presented with low back pain. She had undergone ventriculoperitoneal shunt placement 8 years ago. I scored 76 on the Wechsler Adult Intelligence Scale. MRI of the lumbar spine showed spinal canal stenosis at L3/4, L4/5, and L5/S1. Full spine X-ray revealed thoracic lordosis and lumbar kyphoscoliosis， the coronal imbalance, and the sagittal compensatory balance. In order to avoid the risk of brain swelling and paraplegia, pedicle subtraction osteotomies (PSO) in the L2 and lumbar posterior instrumented scoliosis correction were performed under electroencephalogram and neuro electrophysiological monitoring. Shoulder imbalance was observed 1 year after surgery, but there was no loss of lumbar correction. Conclusion: In future cases of complex spinal deformity, it is important to observe whether there is cerebral ventricular dilatation on MRI before the operation. If severe thoracic lordosis is combined with lumbar scoliosis, over-correcting the lumbar scoliosis should be avoided to prevent shoulder imbalance.

In-office Maximal Voluntary Ventilation Testing Demonstrates Pulmonary Improvement Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

OBJECTIVE: Pulmonary function can be impaired in patients with adolescent idiopathic scoliosis (AIS). Maximal voluntary ventilation (MVV) has been shown to be more strongly correlated with major coronal curve, and a more easily obtained measurement of pulmonary function, than forced vital capacity (FVC). We evaluated changes in pulmonary function using these 2 measures in patients with AIS in relation to changes in major coronal curves over time. METHODS: Forty-seven patients with AIS with thoracic curves ≥10 degrees performed pulmonary function tests using the Carefusion MicroLoop Spirometer at enrollment and 1 year later. Major coronal curve worsening >5 degrees was considered curve progression. RESULTS: At enrollment, 47 patients had a mean major coronal curve of 38 degrees (range: 10 to 76 degrees). One year later, 17 patients had undergone posterior spinal fusion, 9 had curve progression >5 degrees, and 21 had no progression. MVV and major coronal curve were negatively correlated (r = -0.36, P = 0.01) at enrollment. After fusion, the major coronal curve improved by a mean of 41 degrees, and MVV improved by 23% (P < 0.01), but FVC did not improve significantly (6%, P = 0.29). In stable curves, MVV improved 12% (P = 0.01) and FVC improved 9% (P = 0.007). In patients without surgery whose curves progressed an average of 11 degrees, there was no significant change in MVV or FVC (P > 0.44). CONCLUSION: This is the first study using office-based spirometry in an orthopaedic clinic showing improved pulmonary function with posterior spinal fusion and growth in patients with AIS. It is notable that MVV improved after spinal fusion, but FVC did not, as MVV appears to be a more sensitive measurement for the assessment of pulmonary function in these patients. LEVEL OF EVIDENCE: Level II.

Novel Surface Topographic Assessment of Lung Volume and Pulmonary Function Tests in Idiopathic Scoliosis: A Preliminary Study.

OBJECTIVE: Severe spinal deformity results in restrictive pulmonary disease from thoracic distortions and lung-volume limitations. Though spirometry and body plethysmography are widely accepted tests for pulmonary function tests (PFTs), they are time-consuming and require patient compliance. This study investigates whether surface topographic [surface topography (ST)] measurements of body volume difference (BVD) and torso volume difference between maximum inhale and exhale correlate to values determined on PFTs. METHODS: This study included patients with idiopathic scoliosis and thoracic/thoracolumbar curves ≥40 degrees. Patients received ST scans, clinical examinations, and EOS biplanar radiographs on the same day. PFTs were performed within 3 months of ST/radiographic analysis. Univariate linear regression analysis was used to examine relationships between BVD, PFT values, and mean curves. RESULTS: Sixteen patients (14.6 ± 2.2 y, 69% females) with idiopathic scoliosis and mean thoracic/thoracolumbar curves of 62 degrees ± 15˚ degrees (45 degrees to 93 degrees) were assessed. BVD displayed statistically high-positive positive correlations with forced vital capacity ( R = 0.863, P < 0.0001), forced expiratory volume in 1 second ( R = 0.870, P < 0.001), vital capacity ( R = 0.802, P < 0.0001), and TLC ( R = 0.831, P < 0.0001. Torso volume difference showed similarly high positive correlations to forced vital capacity, forced expiratory volume in 1 second, vital capacity, and TLC, but not residual volume. No correlations emerged between the mean thoracic/thoracolumbar curve and BVD or PFT values. CONCLUSION: This study strongly endorses further investigation into ST scanning as an alternative to traditional PFTs for assessing pulmonary volumes. The noncontact and noninvasive nature of ST scanning presents a valuable alternative method for analyzing thoracic volume, particularly beneficial for patients unable to cooperate with standard PFTs. LEVEL OF EVIDENCE: Level II-prognostic.

Explainable Deep-Learning-Based Gait Analysis of Hip-Knee Cyclogram for the Prediction of Adolescent Idiopathic Scoliosis Progression.

Accurate prediction of scoliotic curve progression is crucial for guiding treatment decisions in adolescent idiopathic scoliosis (AIS). Traditional methods of assessing the likelihood of AIS progression are limited by variability and rely on static measurements. This study developed and validated machine learning models for classifying progressive and non-progressive scoliotic curves based on gait analysis using wearable inertial sensors. Gait data from 38 AIS patients were collected using seven inertial measurement unit (IMU) sensors, and hip-knee (HK) cyclograms representing inter-joint coordination were generated. Various machine learning algorithms, including support vector machine (SVM), random forest (RF), and novel deep convolutional neural network (DCNN) models utilizing multi-plane HK cyclograms, were developed and evaluated using 10-fold cross-validation. The DCNN model incorporating multi-plane HK cyclograms and clinical factors achieved an accuracy of 92% in predicting curve progression, outperforming SVM (55% accuracy) and RF (52% accuracy) models using handcrafted gait features. Gradient-based class activation mapping revealed that the DCNN model focused on the swing phase of the gait cycle to make predictions. This study demonstrates the potential of deep learning techniques, and DCNNs in particular, in accurately classifying scoliotic curve progression using gait data from wearable IMU sensors.

[Gait Analysis in Patients with Adolescent Idiopathic Scoliosis]. / Analýza chuze u pacientu s adolescentní idiopatickou skoliózou.

PURPOSE OF THE STUDY: The study describes changes in gait parameters (temporal-spatial parameters, kinematic parameters represented by the global Gait Deviation Index) of individuals with Adolescent Idiopathic Scoliosis (AIS) compared to the healthy population. The hypothesis assumed a difference in the observed parameters between the two mentioned groups. MATERIAL AND METHODS: In a retrospective study, the temporal-spatial parameters and Gait Deviation Index (GDI) of a cohort of 45 AIS patients (36 girls and 9 boys with the mean age of 15.2 years, the mean Cobb angle of the thoracic curve of 47.3° and the lumbar curve of 51.8°) were compared to a typically developing population of 12 healthy individuals with no musculoskeletal pathology. The difference of followed-up parameters in patients with AIS compared to normal values was assessed by one-sample Student's T-test at the significance level of p = 0.05. RESULTS: The gait analysis shows significant deviations in the gait stereotype of patients with AIS compared to the healthy population. Statistically significant differences within temporal-spatial parameters were confirmed for cadence, walking speed, step time, stride time for left leg, step length, stride length and step width. The mean GDI of the cohort reached the value of 91.07 that indicates a slight alteration of gait, however, even this change is statistically significant. DISCUSSION: In our cohort of patients with AIS, we identified a significantly reduced walking speed (on average 15.4% compared to normal values. At the same time, a reduction in cadence (by an average of 7.5%) and an increase of the stride time (by an average of 12%) were recorded. Our mean GDI values were 91.07, which is consistent with the results reported in the literature for comparable groups of AIS patients. CONCLUSIONS: Our study demonstrated that AIS significantly affects gait stereotype. The differences compared to the group of healthy individuals within temporal-spatial parameters were confirmed for cadence, walking speed, duration and length of step and stride, and step width. The kinematic analysis of gait using the global (GDI) index in patients with AIS demonstrated its slight alteration. A better understanding of the change in movement stereotypes and gait in patients with AIS can bring wider possibilities for individualizing conservative treatment and also can help prevent secondary changes in the locomotor system. KEY WORDS: adolescent idiopathic scoliosis, AIS, gait analysis, Gait Deviation Index, GDI.

Effects of a Long-Term Supervised Schroth Exercise Program on the Severity of Scoliosis and Quality of Life in Individuals with Adolescent Idiopathic Scoliosis: A Randomized Clinical Trial Study.

Background and Objectives: Adolescent Idiopathic Scoliosis (AIS) affects individuals aged 10-18 years and is characterized by spinal deformity, three-dimensional axis deformation, and vertebral rotation. Schroth method exercises and braces have been shown to reduce the Cobb angle and halt spinal deformity progression. The aim of this study was to investigate the impact of a 12-month, supervised Schroth exercise program on scoliosis severity and quality of life in adolescents with AIS. Materials and Methods: Eighty adolescents with AIS (aged 10-17 years) were prescribed a brace and were divided into two groups. The intervention group followed a supervised Schroth exercise program three times a week for 12 months in addition to wearing a brace. The control group used only the brace. Outcomes included the Cobb angle of the main curvature and the sum of curves using radiography, the maximum angle of trunk rotation (ATR maximum, using a scoliometer), and quality of life with the Scoliosis Research Society-22 (SRS-22) questionnaire. Evaluations were conducted at baseline, after 12 months, and 6 months post-intervention. A multivariate analysis of covariance (MANCOVA) was used for statistical analysis (p-Value < 0.05). Results: The intervention group showed statistically significant improvement compared to the control group in the 12th month in Cobb angle (mean differences, 95% CI: -3.65 (-5.81, -1.53), p-Value < 0.001, Cohen's d = 0.30), ATR maximum (mean differences, 95% CI: -3.05 (-3.86, -2.23), p-Value < 0.001, Cohen's d = 0.74), and SRS-22 score (mean differences, 95% CI: 0.87 (0.60, 1.13), p-Value < 0.001, Cohen's d = 0.58). Differences in ATR maximum and SRS-22 score remained significant at the 18-month measurement. No significant differences were found between groups in the sum of curves (p-Value > 0.05). Conclusions: A 12-month supervised Schroth exercise program in AIS patients undergoing brace treatment significantly improves scoliosis severity (Cobb angle and ATR maximum) and quality of life. Improvements were greater than those in shorter-duration studies, suggesting a linear dose-response relationship. Further clinical studies are needed to clarify the impact of long-term Schroth programs.

The axonemal dynein heavy chain 10 gene is essential for monocilia motility and spine alignment in zebrafish.

Adolescent idiopathic scoliosis (AIS) is a common pediatric musculoskeletal disorder worldwide, characterized by atypical spine curvatures in otherwise healthy children. Human genetic studies have identified candidate genes associated with AIS, however, only a few of these have been shown to recapitulate adult-viable scoliosis in animal models. Using an F0 CRISPR screening approach in zebrafish, we demonstrate that disruption of the dynein axonemal heavy chain 10 (dnah10) gene results in recessive adult-viable scoliosis in zebrafish. Using a stably segregating dnah10 mutant zebrafish, we showed that the ependymal monocilia lining the hindbrain and spinal canal displayed reduced beat frequency, which was correlated with the disassembly of the Reissner fiber and the onset of body curvatures. Taken together, these results suggest that monocilia function in larval zebrafish contributes to the polymerization of the Reissner fiber and straightening of the body axis.

Association between lean mass and adolescent idiopathic scoliosis: a meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to evaluate the association between lean mass and adolescent idiopathic scoliosis (AIS). METHODS: English databases CENTRAL (The Cochrane Library and the Cochrane Back Review Group Trials Register), MEDLINE, EMBASE, PubMed, Web of Science and Chinese databases CBM, CNKI, VIP, WANGFANG DATA were searched for the relevant case control studies and cross-sectional studies. Two authors selected studies and extracted data independently. Data analysis was performed by Stata15.0. RESULTS: Eight studies were included, with a total of 1771 cases of AIS and 6340 controls. AIS group had a lower lean mass compared to control group [MD = - 1.95, 95% CI (- 2.96, - 0.93)]. In the subgroup analysis, female AIS patients had a lower lean mass than the control group [MD = - 1.76, 95% CI (- 2.63, - 0.88)]. The mean difference of lean mass between AIS patients and control group in studies with adults [MD = - 3.96, 95% CI (- 7.26, - 0.67)] is much greater than studies without adults [MD = - 1.04, 95% CI (- 1.59, - 0.49)]. There was not statistically significant in European studies [MD = - 2.10, 95% CI (- 4.35, 0.14)], but in Asian studies lean mass in AIS patients was lower than the control group [MD = - 2.26, 95% CI (- 3.98, - 0.54)]. Study type, gender, age, and geography condition were thought to have no effect on the primary outcome of lean mass by subgroup analysis. CONCLUSION: In the meta-analysis, AIS group had a lower lean mass compared to control group, which indicated that lean mass may be involved in the pathogenesis of AIS. But limited by the number of studies we included; the above conclusions need to be validated by more high-quality studies.

TBX6 compound inheritance leads to congenital vertebral malformations in humans and mice.

Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. <50%) as a potential mechanism of TBX6-associated CVMs. To further investigate this pathogenetic model, we ascertained and collected 108 Chinese CVM cases and found that 10 (9.3%) of them carried TBX6 null mutations in combination with common hypomorphic variants at the second TBX6 allele. For in vivo functional verification and genetic analysis of TBX6 compound inheritance, we generated both null and hypomorphic mutations in mouse Tbx6 using the CRISPR-Cas9 method. These Tbx6 mutants are not identical to the patient variants at the DNA sequence level, but instead functionally mimic disease-associated TBX6 variants. Intriguingly, as anticipated by the compound inheritance model, a high penetrance of CVM phenotype was only observed in the mice with combined null and hypomorphic alleles of Tbx6. These findings are consistent with our experimental observations in humans and supported the dosage effect of TBX6 in CVM etiology. In conclusion, our findings in the newly collected human CVM subjects and Tbx6 mouse models consistently support the contention that TBX6 compound inheritance causes CVMs, potentially via a gene dosage-dependent mechanism. Furthermore, mouse Tbx6 mutants mimicking human CVM-associated variants will be useful models for further mechanistic investigations of CVM pathogenesis in the cases associated with TBX6.

X-linked frontometaphyseal dysplasia with severe scoliosis and spinal cord compromise in an Indian boy.

Frontometaphyseal dysplasia (FMD) is a rare genetic disorder with morphological abnormalities of the skeletal and extra skeletal tissues. It belongs to the group of otopalatodigital spectrum disorders. Here we report a 12-year-old boy from India with features of frontometaphyseal dysplasia who had severe scoliosis with neurological complications due to spinal cord compromise. Clinical examination of his mother also revealed mild features of FMD. The manuscript highlights the clinical presentation of the disorder and discusses the clinical heterogeneity of the otopalatodigital spectrum disorders.

Common pathogenesis for sirenomelia, OEIS complex, limb-body wall defect, and other malformations of caudal structures.

Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.

Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.