Exome sequencing of 1190 non-syndromic clubfoot cases reveals HOXD12 as a novel disease gene.

BACKGROUND: Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants in known clubfoot disease genes account for only a small portion of the heritability. METHODS: Exome sequence data were generated from 1190 non-syndromic clubfoot cases and their family members from multiple ethnicities. Ultra-rare variant burden analysis was performed comparing 857 unrelated clubfoot cases with European ancestry with two independent ethnicity-matched control groups (1043 in-house and 56 885 gnomAD controls). Additional variants in prioritised genes were identified in a larger cohort, including probands with non-European ancestry. Segregation analysis was performed in multiplex families when available. RESULTS: Rare variants in 29 genes were enriched in clubfoot cases, including PITX1 (a known clubfoot disease gene), HOXD12, COL12A1, COL9A3 and LMX1B. In addition, rare variants in posterior HOX genes (HOX9-13) were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry. Among these, 3 are de novo and 22 show variable penetrance, including 4 HOXD12 variants that segregate with clubfoot. CONCLUSION: We report HOXD12 as a novel clubfoot disease gene and demonstrate a phenotypic expansion of known disease genes (myopathy gene COL12A1, Ehlers-Danlos syndrome gene COL9A3 and nail-patella syndrome gene LMX1B) to include isolated clubfoot.

BrAIST-Calc: Prediction of Individualized Benefit From Bracing for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data. OBJECTIVE: Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence. To avoid over-treatment and to promote patient goal setting and adherence, bracing decisions (who and how much) should be based on physician and patient discussions informed by individual-level data from high-quality predictive models. MATERIALS AND METHODS: Logistic regression was used to predict curve progression to <45° at skeletal maturity (good prognosis) in 269 BrAIST subjects who were observed or braced. Predictors included age, sex, body mass index, Risser stage, Cobb angle, curve pattern, and treatment characteristics (hours of brace wear and in-brace correction). Internal and external validity were evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n=299) through estimates of discrimination and calibration. RESULTS: The final model included age, sex, body mass index, Risser stage, Cobb angle, and hours of brace wear per day. The model demonstrated strong discrimination ( c -statistics 0.83-0.87) and calibration in all data sets. Classifying patients as low risk (high probability of a good prognosis) at the probability cut point of 70% resulted in a specificity of 92% and a positive predictive value of 89%. CONCLUSION: This externally validated model can be used by clinicians and families to make informed, individualized decisions about when and how much to brace to avoid progression to surgery. If widely adopted, this model could decrease overbracing of AIS, improve adherence, and, most importantly, decrease the likelihood of spinal fusion in this population.

Effect of Length Stability on Complications in the Treatment of Preadolescent Diaphyseal Femur Fractures Treated With Elastic Stable Intramedullary Nailing.

OBJECTIVES: To examine the effectiveness and complication rates in age- and size-appropriate patients with either stable or unstable fracture patterns treated with elastic stable intramedullary nailing (ESIN). DESIGN: Retrospective case series. SETTING: Academic tertiary care children's hospital. PATIENTS/PARTICIPANTS: This was a consecutive series of 106 preadolescent children with femoral shaft fractures. The mean age of the patients was 8.0 years (range, 4.0-16.0 years). INTERVENTION: All children were treated by retrograde ESIN. MAIN OUTCOME MEASURES: Fractures were categorized as either length stable or unstable. Length stability and complications were assessed. A subset of patients with final full-length, standing x-rays was also evaluated. RESULTS: We analyzed 63 stable and 43 length unstable fractures. The mean age and weight of the patients with stable and unstable fractures were similar. There was no difference in complication rates between groups (χ2(1) = 0.00, P = 0.99). There was no difference (t(96.93) = 0.53, P = 0.59) in femoral shaft length change. Leg length discrepancies as assessed by full-length standing radiographs at follow-up were similar (χ2(2) = 1.52, P = 0.47). CONCLUSIONS: Preadolescent children younger than 10 years do not experience increased complications after ESIN of length unstable femur fractures [odds ratio (OR) = 1.68 (0.18-16.87), P = 0.65]. Length unstable femur fractures are not at increased risk of more complications [OR = 0.90 (0.26-2.92), P = 0.87], early femoral shortening [OR = (0.42-2.02), P = 0.85], or leg length discrepancy [OR = (0.13-1.56), P = 0.21] when treated with ESIN. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for complete description of levels of evidence.

A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2-directed myogenesis.

Nemaline myopathy (NM) is the most common congenital myopathy, characterized by extreme weakness of the respiratory, limb, and facial muscles. Pathogenic variants in Tropomyosin 2 (TPM2), which encodes a skeletal muscle-specific actin binding protein essential for sarcomere function, cause a spectrum of musculoskeletal disorders that include NM as well as cap myopathy, congenital fiber type disproportion, and distal arthrogryposis (DA). The in vivo pathomechanisms underlying TPM2-related disorders are unknown, so we expressed a series of dominant, pathogenic TPM2 variants in Drosophila embryos and found 4 variants significantly affected muscle development and muscle function. Transient overexpression of the 4 variants also disrupted the morphogenesis of mouse myotubes in vitro and negatively affected zebrafish muscle development in vivo. We used transient overexpression assays in zebrafish to characterize 2 potentially novel TPM2 variants and 1 recurring variant that we identified in patients with DA (V129A, E139K, A155T, respectively) and found these variants caused musculoskeletal defects similar to those of known pathogenic variants. The consistency of musculoskeletal phenotypes in our assays correlated with the severity of clinical phenotypes observed in our patients with DA, suggesting disrupted myogenesis is a potentially novel pathomechanism of TPM2 disorders and that our myogenic assays can predict the clinical severity of TPM2 variants.

Diagnostic yield of exome sequencing in congenital vertical talus.

BACKGROUND: Congenital vertical talus (CVT), also known as "rocker-bottom foot", is a rare foot deformity associated with a dislocation of the talonavicular joint. Although genetic causes of CVT have been described in single isolated and syndromic families, whole-exome sequencing (WES) of large cohorts have not yet been reported. METHODS: In this study, 62 probands with CVT were evaluated for likely causative single nucleotide variants (SNVs) and copy number variants (CNVs) using WES. Segregation of variants within families was determined by Sanger sequencing. RESULTS: In this cohort, CVT occurred as an isolated anomaly in 75.8% (47/62) and was familial in 19.3% (12/62) of cases. Analysis of WES data led to the identification of likely causative variants in known disease genes in 30.6% (19/62) of all CVT probands. More than one proband had likely causative SNVs in TSHZ1, GDF5, and LMX1B. Only two probands had likely causative CNVs: a chromosome 12q13.13 deletion of the 5' HOXC gene cluster, and a chromosome 18q22.3q23 deletion involving TSHZ1. Familial CVT was strongly predictive of identifying a molecular diagnosis [75% (9/12) of familial cases compared to 20% (10/50) of non-familial cases (Chi-square test, P-value = 0.0002)]. There was no difference in the solved rate based on isolated or syndromic presentation, unilateral or bilateral affectation, or sex. CONCLUSIONS: CVT is genetically heterogeneous and more often caused by SNVs than CNVs. There is a high yield of WES in familial CVT cases (∼75%). Additional research is needed to identify the causes of sporadic CVT, which had much lower solved rates.

Whole Exome Sequencing in Individuals with Idiopathic Clubfoot Reveals a Recurrent Filamin B (FLNB) Deletion.

BACKGROUND: Clubfoot, a congenital deformity that presents as a rigid, inward turning of the foot, affects approximately 1 in 1000 infants and occurs as an isolated birth defect in 80% of patients. Despite its high level of heritability, few causative genes have been identified, and mutations in known genes are only responsible for a small portion of clubfoot heritability. QUESTIONS/PURPOSES: (1) Are any rare gene variants enriched (that is, shared) in unrelated patients with isolated clubfoot? (2) Are there other rare variants in the identified gene (Filamin B) in these patients with clubfoot? METHODS: Whole-exome sequence data were generated from a discovery cohort of 183 unrelated probands with clubfoot and 2492 controls. Variants were filtered with minor allele frequency < 0.02 to identify rare variants as well as small insertions and deletions (indels) resulting in missense variants, nonsense or premature truncation, or in-frame deletions. A candidate deletion was then genotyped in another cohort of 974 unrelated patients with clubfoot (a replication cohort). Other rare variants in the candidate gene were also investigated. A segregation analysis was performed in multigenerational families of individuals with clubfoot to see if the genotypes segregate with phenotypes. Single-variant association analysis was performed using the Fisher two-tailed exact test (exact p values are presented to give an indication of the magnitude of the association). RESULTS: There were no recurrent variants in the known genes causing clubfoot in this study. A three-base pair in-frame codon deletion of Filamin B (FLNB) (p.E1792del, rs1470699812) was identified in 1.6% (3 of 183) of probands with clubfoot in the discovery cohort compared with 0% of controls (0 of 2492) (odds ratio infinity (inf) [95% CI 5.64 to inf]; p = 3.18 x 10-5) and 0.0016% of gnomAD controls (2 of 125,709) (OR 1.01 x 103 [95% CI 117.42 to 1.64 x 104]; p = 3.13 x 10-8). By screening a replication cohort (n = 974 patients), we found two probands with the identical FLNB deletion. In total, the deletion was identified in 0.43% (5 of 1157) of probands with clubfoot compared with 0% of controls and 0.0016% of gnomAD controls (OR 268.5 [95% CI 43.68 to 2.88 x 103]; p = 1.43 x 10-9). The recurrent FLNB p.E1792del variant segregated with clubfoot, with incomplete penetrance in two families. Affected individuals were more likely to be male and have bilateral clubfoot. Although most patients had isolated clubfoot, features consistent with Larsen syndrome, including upper extremity abnormalities such as elbow and thumb hypermobility and wide, flat thumbs, were noted in affected members of one family. We identified 19 additional rare FLNB missense variants located throughout the gene in patients with clubfoot. One of these missense variants, FLNB p.G2397D, exhibited incomplete penetrance in one family. CONCLUSION: A recurrent FLNB E1792 deletion was identified in 0.43% of 1157 isolated patients with clubfoot. Given the absence of any recurrent variants in our discovery phase (n = 183) for any of the known genes causing clubfoot, our findings support that novel and rare missense variants in FLNB in patients with clubfoot, although rare, may be among the most commonly known genetic causes of clubfoot. Patients with FLNB variants often have isolated clubfoot, but they and their family members may be at an increased risk of having additional clinical features consistent with Larsen syndrome. CLINICAL RELEVANCE: Identification of FLNB variants may be useful for determining clubfoot recurrence risk and comorbidities.

Clubfoot.

Clubfoot or talipes equinovarus deformity is one of the most common anomalies affecting the lower extremities. This review provides an update on the outcomes of various treatment options used to correct clubfoot. The ultimate goal in the treatment of clubfoot is to obtain a fully functional and pain-free foot and maintain a long-term correction. The Ponseti method is now considered the gold standard of treatment for primary clubfoot. Relapse is common after primary treatment with the Ponseti method, and other interventions are discussed that are used to provide for long-term successful outcomes.

A Decade in Review after Idiopathic Scoliosis Was First Called a Complex Trait-A Tribute to the Late Dr. Yves Cotrel for His Support in Studies of Etiology of Scoliosis.

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model for AIS. Here, we review in detail the vast information about the genetic and environmental factors in AIS pathogenesis gathered to date. More importantly, new insights into AIS etiology were brought to us through new research data under the perspective of a complex trait. Hopefully, future research directions may lead to better management of AIS, which has a tremendous impact on affected adolescents in terms of both physical growth and psychological development.

Models of Distal Arthrogryposis and Lethal Congenital Contracture Syndrome.

Distal arthrogryposis and lethal congenital contracture syndromes describe a broad group of disorders that share congenital limb contractures in common. While skeletal muscle sarcomeric genes comprise many of the first genes identified for Distal Arthrogyposis, other mechanisms of disease have been demonstrated, including key effects on peripheral nerve function. While Distal Arthrogryposis and Lethal Congenital Contracture Syndromes display superficial similarities in phenotype, the underlying mechanisms for these conditions are diverse but overlapping. In this review, we discuss the important insights gained into these human genetic diseases resulting from in vitro molecular studies and in vivo models in fruit fly, zebrafish, and mice.

Genetic association and characterization of FSTL5 in isolated clubfoot.

Talipes equinovarus (clubfoot, TEV) is a congenital rotational foot deformity occurring in 1 per 1000 births with increased prevalence in males compared with females. The genetic etiology of isolated clubfoot (iTEV) remains unclear. Using a genome-wide association study, we identified a locus within FSTL5, encoding follistatin-like 5, significantly associated with iTEV. FSTL5 is an uncharacterized gene whose potential role in embryonic and postnatal development was previously unstudied. Utilizing multiple model systems, we found that Fstl5 was expressed during later stages of embryonic hindlimb development, and, in mice, expression was restricted to the condensing cartilage anlage destined to form the limb skeleton. In the postnatal growth plate, Fstl5 was specifically expressed in prehypertrophic chondrocytes. As Fstl5 knockout rats displayed no gross malformations, we engineered a conditional transgenic mouse line (Fstl5LSL) to overexpress Fstl5 in skeletal osteochondroprogenitors. We observed that hindlimbs were slightly shorter and that bone mineral density was reduced in adult male, but not female, Prrx1-cre;Fstl5LSL mice compared with control. No overt clubfoot-like deformity was observed in Prrx1-cre;Fstl5LSL mice, suggesting FSTL5 may function in other cell types to contribute to iTEV pathogenesis. Interrogating published mouse embryonic single-cell expression data showed that Fstl5 was expressed in cell lineage subclusters whose transcriptomes were associated with neural system development. Moreover, our results suggest that lineage-specific expression of the Fstl genes correlates with their divergent roles as modulators of transforming growth factor beta and bone morphogenetic protein signaling. Results from this study associate FSTL5 with iTEV and suggest a potential sexually dimorphic role for Fstl5 in vivo.

Rare and de novo coding variants in chromodomain genes in Chiari I malformation.

Chiari I malformation (CM1), the displacement of the cerebellum through the foramen magnum into the spinal canal, is one of the most common pediatric neurological conditions. Individuals with CM1 can present with neurological symptoms, including severe headaches and sensory or motor deficits, often as a consequence of brainstem compression or syringomyelia (SM). We conducted whole-exome sequencing (WES) on 668 CM1 probands and 232 family members and performed gene-burden and de novo enrichment analyses. A significant enrichment of rare and de novo non-synonymous variants in chromodomain (CHD) genes was observed among individuals with CM1 (combined p = 2.4 × 10-10), including 3 de novo loss-of-function variants in CHD8 (LOF enrichment p = 1.9 × 10-10) and a significant burden of rare transmitted variants in CHD3 (p = 1.8 × 10-6). Overall, individuals with CM1 were found to have significantly increased head circumference (p = 2.6 × 10-9), with many harboring CHD rare variants having macrocephaly. Finally, haploinsufficiency for chd8 in zebrafish led to macrocephaly and posterior hindbrain displacement reminiscent of CM1. These results implicate chromodomain genes and excessive brain growth in CM1 pathogenesis.

MYH3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin.

Distal arthrogryposis (DA) is group of syndromes characterized by congenital joint contractures. Treatment development is hindered by the lack of vertebrate models. Here, we describe a zebrafish model in which a common MYH3 missense mutation (R672H) was introduced into the orthologous zebrafish gene smyhc1 (slow myosin heavy chain 1) (R673H). We simultaneously created a smyhc1 null allele (smyhc1- ), which allowed us to compare the effects of both mutant alleles on muscle and bone development, and model the closely related disorder, spondylocarpotarsal synostosis syndrome. Heterozygous smyhc1R673H/+ embryos developed notochord kinks that progressed to scoliosis with vertebral fusions; motor deficits accompanied the disorganized and shortened slow-twitch skeletal muscle myofibers. Increased dosage of the mutant allele in both homozygous smyhc1R673H/R673H and transheterozygous smyhc1R673H/- embryos exacerbated the notochord and muscle abnormalities, causing early lethality. Treatment of smyhc1R673H/R673H embryos with the myosin ATPase inhibitor, para-aminoblebbistatin, which decreases actin-myosin affinity, normalized the notochord phenotype. Our zebrafish model of MYH3-associated DA2A provides insight into pathogenic mechanisms and suggests a beneficial therapeutic role for myosin inhibitors in treating disabling contractures.

Selective Dorsal Rhizotomy for the Treatment of Spastic Hemiplegic Cerebral Palsy.

Background Selective dorsal rhizotomy (SDR) can remove spasticity in cerebral palsy (CP). Spastic hemiplegia is associated with spasticity in the upper and lower limbs on one side. Only a single report described the outcome of SDR specifically in patients with spastic hemiplegic CP. The effect of SDR on spastic hemiplegia requires further investigation. Objectives To analyze the outcomes of motor functions, the quality of life, and satisfaction of patients who received SDR for the treatment of spastic hemiplegia. Methods A total of 29 children and 1 adult who received SDR were surveyed. The survey questionnaire asked about demographic information, patient's perception of SDR, functional outcomes, SDR surgical outcomes, pain, braces/orthotics, and post-SDR treatment. Results Our study included 30 patients. The age at the time of surgery was 2 to 36 years. The follow-up period ranged from one to six years. Of all parents, 90% of parents reported that SDR benefited their children, and 93% stated that they would recommend the SDR procedure to other families of children with hemiplegic CP. Of all patients, 90% reported improved walking, 63% reported improved sitting, and 87% reported improved balance and posture. In daily life functioning after the SDR, 67% were more independent and confident. Moreover, 33% of patients were pain-free and 43% had reduced pain in their legs and back. In activities of daily living, 93% transferred independently from one position to another. A majority of the patients reported regular strengthening and stretching of the lower limb, and 50% of the patients played sports. A majority (73%) of patients underwent post-SDR orthopedic surgery for heel cord, hamstring, and adductor contractures. Five patients experienced numbness in the small part of the lower limb after SDR. None reported that the numbness affected their daily activities. One child required surgical repair of the cerebrospinal fluid leak. Conclusions In our 29 children and 1 adult with spastic hemiplegia, SDR improved motor function and daily life function. Nearly all parents of children and the one adult felt that SDR was beneficial and that they would recommend surgery to other children with spastic hemiplegia.

Selective Dorsal Rhizotomy for the Treatment of Spastic Triplegic Cerebral Palsy.

Background Spastic triplegia is a recognized subtype of cerebral palsy (CP). In the course of treating spastic triplegic children with selective dorsal rhizotomy (SDR), we found that some children who had "minimal or mild involvement" in the stronger arm improved strikingly after undergoing SDR. Some of them became independent ambulators, which was an outcome that is not usually achieved in spastic quadriplegic children. However, the literature currently contains no data on the natural clinical course and the effects of CP interventions on spastic triplegia. Objectives Our aim was to elucidate the clinical characteristics of spastic triplegia and the effects of SDR on functional outcomes and the quality of life after childhood SDR. Methods The Institutional Review Board of the Washington University School of Medicine approved this quality of life survey (number: 201908177). The subjects of this study were children and adults (ages: 3.9-23.8 years at the time of the survey completion; mean: 12.1 ± 5.1 years) with spastic triplegic CP who had undergone SDR (ages: 2.2-15.9 years; mean: 6.1 ± 3.2 years) between 2003 and 2018 at the St. Louis Children's Hospital. The follow-up period ranged from 1-16 years (mean: 6.0 ± 4.3 years). The study included a 76-patient cohort selected from a total of 253 spastic triplegic CP patients who had undergone SDR. All 253 patients were contacted via email or postal mail soliciting their participation in the study including the survey. The cohort included all patients who responded. The survey included questions on demographic information, quality of life, perceptions of health and the SDR procedure, motor and ambulatory functions, braces and orthotics, pain issues, side effects of SDR, and post-SDR treatment. Results Thirteen patients had presented with scissored gait, and these patients had undergone partial ventral rhizotomy (PVR) of L1-3 ventral roots immediately after the completion of SDR. Of note, 91% of 76 patients reported that SDR improved their quality of life, and 93% would recommend the procedure to other patients. After SDR, 21 more patients were able to run, 14 more played recreational sports, and 18 more could walk without using walking aids. Sixteen fewer patients used a wheelchair for long-distance walking and in crowds; 37 and 32 patients reported an improvement in the more affected arm and hand, respectively. Sixty-eight patients were able to regularly strengthened their muscles at least once a week, and 60 patients regularly stretched their legs. However, 53 patients required assistance with bathing or showering, 50 with getting dressed, and 56 with grooming or hygiene. Forty-eight patients had orthopedic surgery after SDR. Percutaneous hamstring-lengthening was the most common type of orthopedic surgery performed. Three of 13 patients who received PVR and SDR required adductor release. Six patients used medications for spasticity or dystonia. No late side effects of SDR were observed. Conclusions Our report elucidates the clinical features of spastic triplegia before and after SDR. A distinct clinical feature was the wide variation in ambulatory functions, ranging from total independent walking to wheelchair mobility. The vast majority of patients felt that SDR improved their motor functions and quality of life. PVR also resulted in favorable outcomes, with only three of 13 patients requiring additional adductor release surgery. There were no late complications related to SDR surgery.

Treatment of femoral fractures in children aged two to six.

AIMS: Current American Academy of Orthopaedic Surgeons (AAOS) guidelines for treating femoral fractures in children aged two to six years recommend early spica casting although some individuals have recommended intramedullary stabilization in this age group. The purpose of this study was to compare the treatment and family burden of care of spica casting and flexible intramedullary nailing in this age group. METHODS: Patients aged two to six years old with acute, non-pathological femur fractures were prospectively enrolled at one of three tertiary children's hospitals. Either early closed reduction with spica cast application or flexible intramedullary nailing was accomplished under general anaesthesia. The treatment method was selected after discussion of the options by the surgeon with the family. Data were prospectively collected on patient demographics, fracture characteristics, complications, pain medication, and union. The Impact on Family Scale was obtained at the six-week follow-up visit. In all, 75 patients were included in the study: 39 in the spica group and 36 in the nailing group. The mean age of the spica group was 2.71 (2.0 to 6.9) years and the mean age of the nailing group was 3.16 (2.0 to 6.9) years. RESULTS: All fractures healed without evidence of malunion or more than 2.0 cm of shortening. The mean Impact on Family score was 70.2 for the spica group and 63.2 (55 to 99) for the nailing group, a statistically significant difference (p = 0.024) in a univariate analysis suggesting less impairment of the family in the intramedullary nailing group. There was no significant difference between pain medication requirements in the first 24 hours postoperatively. Two patients in the spica group and one patient in the intramedullary nailing group required additional treatment under anaesthesia. CONCLUSION: Both early spica casting and intramedullary nailing were effective methods for treating femoral fractures in children two to six years of age. Intramedullary stabilization provides an option in this age group that may be advantageous in some social situations that depend on the child's mobility. Fracture treatment should be individualized based on factors that extend beyond anatomical and biological factors. Cite this article: Bone Joint J 2020;102-B(8):1056-1061.

Improving musculoskeletal health for children and young people - A 'call to action'.

This chapter describes the musculoskeletal (MSK) context in children and young people as an important contributor to the global non-communicable disease burden. Through selected MSK conditions, we describe the impact on patients, families and communities and highlight the challenges that need to be addressed. We focus on opportunities for better working together and describe exemplar initiatives to raise awareness, workforce capacity building, models of care and research agendas to have a greater global context.

The paediatric global musculoskeletal task force - 'towards better MSK health for all'.

There is increasing concern about the emerging global non-communicable diseases (NCDs) burden. The focus has mainly been on NCDs in adults but it is important that MSK morbidity in both children and adults is included in strategic planning. There have been considerable advances in the understanding and treatment options for children and young people (CYP) and clinical outcomes are improving for those who can access such high quality care. However vast inequity exists and there are many CYP who live in areas of the world with high burden of health care challenges, compounded by paucity of specialist care and limited access to treatments. The Paediatric Global Musculoskeletal Task Force aims to raise awareness about unmet needs for CYP with MSK conditions, promotion of MSK health through lifestyle and the avoidance of injury. We aim to leverage change through 'working together better'.