Background. Signalling by growth differentiation factor 6 (GDF6/BMP13) has been implicated in the development and maintenance of healthy NP cell phenotypes and GDF6 mutations are associated with defective vertebral segmentation in Klippel-Feil syndrome. GDF6 may thus represent a promising biologic for treatment of IVD degeneration. This study aimed to investigate the effect of GDF6 in human NP cells and critical signal transduction pathways involved. Methods. BMP receptor expression profile of non-degenerate and degenerate human NP cells was determined through western blot, immunofluorescence and qPCR. Phosphorylation statuses of Smad1/5/9 and non-canonical p38 MAPK and Erk1/2 were assessed in the presence/absence of pathway blockers. NP marker and matrix degrading enzyme gene expression was determined by qPCR following GDF6 stimulation. Glycosaminoglycan and collagen production were assessed through DMMB-assay and histochemical staining. Results. NP cells expressed all GDF6 receptor subunits, with receptor subunits BMPR-1A and BMPR2 displaying the highest expression and highest binding affinity. GDF6 stimulation significantly upregulated the expression of NP specific marker genes but had no significant effect on the expression of matrix degrading enzymes. Total glycosaminoglycan and collagen production was also significantly increased following GDF6 stimulation. Smad1/5/9, p38 MAPK and Erk1/2 pathways were phosphorylated following GDF6 stimulation and could be effectively blocked. Conclusions. These findings enhance our understanding of both the effects of GDF6 in NP cells and the mechanisms of GDF6 signal transduction that are critical to promote NP phenotype and cellular function. This knowledge is important for the effective use of GDF6 as a therapeutic molecule for treatment of IVD degeneration. Conflicts of interest. No conflicts of interest. Sources of funding. We would like to acknowledge UKRMP Acellular Hub, MRC, NIHR Musculoskeletal BRU and The Rosetrees Trust for funding this research

Malformation and hypoplasia of the clavicle can result in pain, impaired function, restricted shoulder movement, subjective feeling of instability and cosmetic deformity. There are no reports of clavicle lengthening by osteotomy and distraction osteogenesis (DO). This is a retrospective review of 5 patients (7 clavicles) who underwent clavicle lengthening by DO using a monolateral external fixator for clavicular hypoplasia. There were 3 males and 2 females with mean age 15 years (9 to 23) and mean follow-up 21 months (8 to 51). Preoperative diagnoses included Klippel-Feil syndrome, cleidocranial dysplasia with torticollis, congenital myopathy and Noonans syndrome and obstetric brachial plexus injury. Mean length gained was 31 mm (15 to 41) which represens an average of 24.7% of overall bone length. Mean time in fixator was 174 days (161 to 263) and mean external fixation index was 56 days/cm. Two patients required internal fixation following fixator removal to consolidate union and one required additional internal fixation for atrophic regenerate. Mean preoperative oxford shoulder score improved from 28.5 to 41 and all patients were extremely satisfied with their result. Two patients developed pin site infections. Clavicular lengthening by distraction osteogenesis for congenital clavicular hypoplasia is a previously unreported technique that enables gradual correction of deformity without risking brachial plexus traction injury following acute correction. It has the potential to improve shoulder pain, function, range of movement and cosmesis. Distraction ≥25% of overall bone length may require additional plate fixation to consolidate union

Introduction and Aims: The anterior approach to dealing with complex spinal deformities around the cervical thoracic junction presents a surgical challenge. With the help of a cardiothoracic surgeon, a sternal splitting technique was utilised in five paediatric patients to resolve this difficulty and gain access to spinal deformities around the cervical thoracic junction. Method: A longitudinal incision is made parallel to the sternocleido muscle and extended across the sternum for a median sternotomy. The sternocleido muscles are retracted to the lateral aspect of the incision. The carotid and jugular vein are dissected out. To continue with the dissection and exposure of the upper thoracic spine, a full sternotomy is done. The sternum is opened. The dissection of the right carotid is extended over the innominate artery, including the bifurcation of the right subclavian artery. The jugular vein is dissected out coming down to the superior vena cava. The innominate vein is isolated. The lower end of the anterior scalenus muscle is divided up. Results: This technique was employed in five paediatric patients, aged three to 15 years, at the authors’ institution. Diagnoses included Klippel-Feil Syndrome, Proteus Syndrome, Larsen Syndrome and, Neurofibromatosis (two patients). All patients had severe cervical thoracic kyphosis requiring surgical instrumentation. This technique resulted in a range of access from C5 to T6 being granted. In one patient, a separate thorocotemy was performed in order to gain access to the lower thoracic spine. Conclusion: This approach was invaluable in gaining access to the cervical thoracic junction to address complex spinal deformities. Access to the lower cervical and the upper thoracic spine is granted. No significant complications occurred. The aid of a cardiothoracic surgeon is advised

Summary of Background Data: The craniofacial malformations described by Goldenhar can be associated with congenital anomalies of the vertebrae. This non-random association of abnormalities represents unilateral errors in the morphogenesis of the spine, as well as the first and second branchial arches. Purpose of the study: The aim of the present study was to determine the prevalence of Goldenhar related conditions in patients with congenital deformities of the spine and to describe the types of vertebral abnormalities and the necessity for treatment. Material-Methods: We performed a retrospective study of 668 consecutive patients with congenital deformities of the spine. The medical records and spinal radiographs were reviewed and patients with a Goldenhar associated condition were identified. The vertebral anomalies causing the spine deformity were detected on antero-posterior and lateral spine radiographs. The type and site of the craniofacial abnormalities, as well as other musculoskeletal deformities and systemic anomalies were recorded. Results: Fourteen patients had Goldenhar associated conditions (7 males and 7 females). A thoracic scoliosis was the most common type of deformity occurring in ten patients (71.5%). Eight of these patients had an isolated hemivertebra and the remaining two had a unilateral unsegmented bar with contralateral hemivertebra at the same level. There was only one patient with a lumbar scoliosis and this was due to a hemivertebra. The side of the vertebral anomaly correlated with that of the hemifacial microsomia in five of the eleven patients who had a scoliosis or kyphoscoliosis. A thoracolumbar kyphosis occurred in four patients; two had posterior hemivertebrae, one had wedge vertebrae, and the remaining patient had an anterior unsegmented bar. A thoracolum-bar kyphoscoliosis occurred in only one patient and was due to a posterolateral quadrant vertebra. Klippel-Feil syndrome occurred in six patients (42.8%). Eight patients (57%) underwent surgical treatment at a mean age of 9.8 years (range: 2.9–19). Four patients had a combined anterior-posterior spine arthrodesis. The remaining four patients had a posterior spinal arthrodesis. Conclusions. The prevalence of Goldenhar associated conditions in patients with congenital deformities of the spine was 2%. Failures of vertebral segmentation were the most frequent abnormality in the cervical spine, whereas failures of vertebral formation most commonly occurred in the thoracic or thoracolumbar spine