Bone allografting: an original method for biological osteosynthesis and bone reinforcement in children with osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) is a genetic disorder responsible for various symptoms including deformities and frequent fractures. Bone allografting is poorly documented in this condition. The objective of this study was to describe our experience and assessments in a consecutive series of OI patients. METHODS: Thirty-nine lower limb allograft procedures (28 femurs, 11 tibias) were performed in 26OI patients (mean age, 12.9 years). They were classified as type III of Sillence (17), type IV (6), and 3 recessive forms. The indications for surgery were correction of deformity (19), fracture (16), and non-union (4). In all cases, bone allografting was added to reinforce areas of fragility and in 28 cases for osteosynthesis to lock the rotations at the osteotomy site and to avoid screwed metallic plate. The duration of bone consolidation and allograft fusion was assessed. Complications and Gillette functional score were reported. RESULTS: The mean follow-up was 6.7years (range, 2 to 10 years). On average, bone consolidation was achieved after 3.3 months and graft fusion after 7.7 months. No bone allograft-related complications were observed and there was any secondary displacement. The Gillette functional score was improved in 23 patients and stable in three cases. Complications were reported in two cases: one partial allograft resorption and one delayed consolidation of a non-union. One refracture was observed but after a significant trauma in a child who had regained significant physical activity. CONCLUSIONS: Bone allografting in children with OI is a reliable method of biological fixation, allowing efficient fusion and contributing to increased bone capital and functional outcome.

[Constitutional diseases of bone: clinical flags]. / Quand penser à une maladie osseuse constitutionnelle ?

Constitutional diseases of bone form a heterogeneous group of rare diseases of varied phenotypic presentations with a vast genetic heterogeneity. Detected mostly in childhood, they may also be diagnosed in adulthood. Medical history, clinical examination as well as biological and radiological investigations may lead to the diagnosis, which should be confirmed genetically. Joint limitations, early osteoarthritis, hip dysplasia, bone deformity, enthesopathies, bone fragility or a small height can be warning signs of a constitutional disease of bone. Establishing the diagnosis is crucial to enable optimal medical management with a specialized multidisciplinary team.

Les maladies osseuses constitutionnelles constituent un groupe hétérogène de maladies rares de présentations phénotypiques variées et d'une grande hétérogénéité génétique. Le plus souvent détectées dans l'enfance, elles peuvent également être diagnostiquées à l'âge adulte. L'anamnèse, l'examen clinique et les bilans biologiques et radiologiques permettent d'orienter le diagnostic, qui devra être confirmé par une analyse génétique. Les limitations articulaires, l'arthrose précoce, les dysplasies de hanches, les déformations osseuses, les enthésopathies ou la fragilité osseuse ainsi qu'une petite taille sont des signes d'alerte pour rechercher une maladie osseuse constitutionnelle. Établir le diagnostic est crucial pour permettre une prise en charge optimale, multidisciplinaire et spécialisée.

Tibial Sliding Elastic Nailing Technique in Moderate-to-Severe Osteogenesis Imperfecta: Long-term Outcomes.

BACKGROUND: Osteosynthesis of leg fractures and deformities in children with osteogenesis imperfecta should align the skeleton and overcome its fragility during growth with a telescopic effect. A high rate of mechanical complications is associated with various surgical techniques described in the literature. PURPOSE: The objective of this work was to assess the long-term clinical and radiologic outcomes of tibial sliding elastic nailing technique. METHODS: A total of 22 children with an average age of 4.7 years were operated using the technique between 2004 and 2018 unilaterally (6) or bilaterally (16), that is, 38 operations. They were listed according to the Sillence classification into type I (3), III (17), or V (2). The nails were introduced percutaneously at the distal tibial epiphysis through the medial malleolus, and in the prespinal area for the proximal tibial epiphysis. The stainless-steel rods diameter was 1.5 to 2.5 mm, adapted to the size and weight of the patient. Realignment osteotomies were performed if necessary. Radiographic data including the correction of the deformation in the frontal and sagittal planes, as well as the width at mid-shaft of the tibia in the frontal and sagittal planes, were reviewed. Gillette Functional Score, assessment of pain, mechanical and infectious complications were collected. RESULTS: The average follow-up was 8.6 years. In the frontal plane, preoperative average varus was 8 degrees (maximum, 40 degrees), 5 degrees (maximum, 13 degrees) postoperatively, and 6 degrees (maximum, 12 degrees) at last follow-up. Preoperative valgus was 11 degrees (maximum, 22 degrees), 9 degrees (maximum, 15 degrees) postoperatively, and 9 degrees (maximum, 14 degrees) at the last follow-up. In the sagittal plane, the mean sagittal bowling of the tibia was 32 degrees (4 to 75 degrees) preoperatively, 9 degree (1 to 26 degrees) postoperatively, and 9 degrees (1 to 24 degrees) at last follow-up. The width at mid-shaft of the tibia in the frontal plane was 1.1 cm (0.6 to 1.8 cm) preoperatively and 1.3 cm at the last follow-up (0.7 to 2.0 cm). In the sagittal plane, it was 1.25 cm (0.7 to 2.7 cm) preoperatively and 1.27 cm (0.8 to 2.8 cm) at the last follow-up. Ten patients did not require revision surgery during their follow-up. Sixteen mechanical complications occurred in 12 patients (12 fractures or deformities following a lack of overlap of the 2 rods at an average time of 4.9 years after the initial surgery, 3 prominence of the nail, 1 pseudarthrosis). No infectious complication was reported. Gillette Functional Score was 20.54/65. Fifteen patients were able to walk at last follow-up, and 18 had no painful discomfort. CONCLUSIONS: The tibial sliding elastic nailing technique provides satisfactory clinical and radiologic results over time. Performed in case of fracture or as a preventive treatment, it allows a good correction of angular deformations. It is particularly suitable for young patients with a narrow medullary shaft. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Geleophysic and acromicric dysplasias: natural history, genotype-phenotype correlations, and management guidelines from 38 cases.

PURPOSE: Geleophysic dysplasia (GD) and acromicric dysplasia (AD) are characterized by short stature, short extremities, and progressive joint limitation. In GD, cardiorespiratory involvement can result in poor prognosis. Dominant variants in the FBN1 and LTBP3 genes are responsible for AD or GD, whereas recessive variants in the ADAMTSL2 gene are responsible for GD only. The aim of this study was to define the natural history of these disorders and to establish genotype-phenotype correlations. METHODS: This monocentric retrospective study was conducted between January 2008 and December 2018 in a pediatric tertiary care center and included patients with AD or GD with identified variants (FBN1, LTBP3, or ADAMTSL2). RESULTS: Twenty-two patients with GD (12 ADAMTSL2, 8 FBN1, 2 LTBP3) and 16 patients with AD (15 FBN1, 1 LTBP3) were included. Early death occurred in eight GD and one AD. Among GD patients, 68% presented with heart valve disease and 25% developed upper airway obstruction. No AD patient developed life-threatening cardiorespiratory issues. A greater proportion of patients with either a FBN1 cysteine variant or ADAMTSL2 variants had a poor outcome. CONCLUSION: GD and AD are progressive multisystemic disorders with life-threatening complications associated with specific genotype. A careful multidisciplinary follow-up is needed.

Sleep-disordered breathing and its management in children with rare skeletal dysplasias.

Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.

Can Chiari Osteotomy Favorably Influence Long-term Hip Degradation in Multiple Epiphyseal Dysplasia and Pseudoachondroplasia?

BACKGROUND: Multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH) are congenital skeletal disorders characterized by irregular epiphyses, mild or severe short stature and early-onset osteoarthritis which frequently affect the hips. The current study evaluates the long-term results of the Chiari osteotomy in MED and PSACH patients. METHODS: Twenty patients (14 MED and 6 PSACH) were retrospectively included. Clinical assessment used the Postel Merle d'Aubigné (PMA) score and the Hip disability and Osteoarthritis Outcome Score (HOOS). Risser index, Sharp angle, acetabular depth index, center-edge angle, Tönnis angle, and femoral head coverage were measured on the preoperative radiographs and at last follow-up. The Treble index, which identifies the hip at risk in MED patients, was also determined. Stulberg classification (grades I to V) was used to evaluate the risk of osteoarthritis in the mature hips.Statistical analyses determined differences between preoperative and postoperative data. The Kaplan Meier method was used to calculate the survival rate of the operated hips using total hip arthroplasty as the endpoint. RESULTS: Thirty-three hips which underwent a Chiari osteotomy were reviewed. The average follow-up was 20.1 years. The PMA scores were significantly better at last follow-up than preoperatively. All radiographic parameters significantly improved. Moreover, the Sharp angle, center-edge angle, and femoral head coverage improved to a normal value at hip maturity. All of the operated hips had a Treble index of type I. At hip maturity, a majority of hip were aspherical congruent (Stulberg grades of III and IV). The survival rate of the operated hips was 80.7% at 24 years postoperative. CONCLUSIONS: The Chiari osteotomy is a satisfying solution for severe symptomatic hip lesions in MED and PSACH patients. At long-term follow-up, this procedure lessens pain and improves hip function, which delays total hip arthroplasty indication. LEVEL OF EVIDENCE: Level IV.

Bone and joint infections in infants under three months of age.

AIM: Studies on bone and joint infections (BJI) in infants under three months are rare. We described the clinical and paraclinical features and outcomes of infants hospitalised with BJI under three months of age. METHODS: The French National Hospital Discharge Database provided data on BJIs in infants under three months of age from January 2004 to 2015 in three Parisian Paediatric teaching hospitals. RESULTS: We included 71 infants under three months of age with BJI, the median age was 25 days, and the interquartile range (IQR) was 17-43 days. The most common infection sites were the hip (32%) and knee (32%). Symptoms included pain (94%), limited mobility (87%) and/or fever (52%). There were 11 (15.5%) cases of nosocomial BJI. A pathogen was identified in 51 infants (71.8%), including Streptococcus agalactiae (45%), Staphylococcus aureus (22%) and Escherichia coli (18%). The initial median C-reactive protein test rate was 31 mg/L (IQR 17-68). Of the 34 infants followed for more than one year, four developed severe orthopaedic conditions such as epiphysiodesis, limb length discrepancy, bone necrosis and/or impaired limb function. CONCLUSION: Streptococcus agalactiae was the most common cause of BJI in infants under three months. Orthopaedic sequelae were rare, but severe, and required long-term follow-up.

Long-Term Results of the "Horseman" Procedure for Severe Idiopathic Flatfoot in Children: A Retrospective Analysis of 41 Consecutive Cases With Mean 8.9 Year Duration of Follow-Up.

The "horseman" procedure is a surgical technique used to correct the talocalcaneal joint displacement of severe idiopathic flatfoot in children while maintaining the reduction with a temporary talocalcaneal screw. While this technique has been used since the early 1960s, very little has been reported on its results. Our objectives were to estimate the correction, functional results, and postoperative complications of the "horseman" procedure. We conducted a retrospective study on 23 consecutive patients (41 cases) who underwent the "horseman" procedure for a talocalcaneal joint displacement. Mean follow-up was 8.9 (range 1 to 28) years, and 8 patients (12 feet) had reached bone maturity at last follow-up. Mean age at surgery was 6.6 (range 4 to 9.5) years. At last follow-up, all the patients were asymptomatic except 2 [8.7%] (4 [9.8%] cases). The talocalcaneal divergence on anteroposterior and lateral radiographic views was reduced by 8.9° and 11.4°, respectively, after the surgery, and the correction was maintained with loss of 0.7° and 2.9°, respectively, at final follow-up. The talonavicular coverage angle was reduced by 25° without loss of correction at last follow-up. The calcaneal pitch angle did not change after the surgery. Mean American Orthopedic Foot and Ankle Society score increased from 88.7 of 100 (63 of 100 to 93 of 100) preoperatively to 99 of 100 (97 to 100 of 100) at last follow-up. No major complication occurred. The "horseman" procedure allows an immediate and lasting correction of severe idiopathic flatfoot in children.

Identification of kinesin family member (KIF22) homozygous variants in spondyloepimetaphyseal dysplasia with joint laxity, lepdodactylic type and demonstration of proteoglycan biosynthesis impairment.

Heterozygous variants in KIF22, encoding a kinesin-like protein, are responsible for spondyloepimetaphyseal dysplasia with joint laxity, leptodactilic type (lepto-SEMDJL), characterized by short stature, flat face, generalized joint laxity with multiple dislocations, and progressive scoliosis and limb deformity. By targeted gene sequencing analysis, we identified a homozygous KIF22 variant (NM_007317.3: c.146G>A, p.Arg49Gln) in 3 patients from 3 unrelated families. The clinical features appeared similar to those of patients carrying heterozygous KIF22 variant (c.443C>T or c.446G>A), although the spinal involvement appeared later and was less severe in patients with a recessive variant. Relatives harboring the c.146G>A variant at the heterozygous state were asymptomatic. The homozygous KIF22 variant c.146G>A affected a conserved residue located in the active site and potentially destabilized ATP binding. RT-PCR and western blot analyses demonstrated that both dominant and recessive KIF22 variants do not affect KIF22 mRNA and protein expression in patient fibroblasts compared to controls. As lepto-SEMDJL presents phenotypic overlap with chondrodysplasias with multiple dislocations (CMD), related to defective proteoglycan biosynthesis, we analyzed proteoglycan synthesis in patient skin fibroblasts. Compared to controls, DMMB assay showed a significant decrease of total sulfated proteoglycan content in culture medium but not in the cell layer, and immunofluorescence demonstrated a strong reduction of staining for chondroitin sulfates but not for heparan sulfates, similarly in patients with recessive or dominant KIF22 variants. These data identify a new recessive KIF22 pathogenic variant and link for the first time KIF22 pathogenic variants to altered proteoglycan biosynthesis and place the lepto-SEMDJL in the CMD spectrum.

Heterozygous variants in KIF22, encoding a kinesin-like protein, are responsible for spondyloepimetaphyseal dysplasia with joint laxity, leptodactilic type (lepto-SEMDJL), characterized by short stature, flat face, generalized joint laxity with multiple dislocations, and progressive scoliosis and limb deformity. We identified a homozygous KIF22 variant (NM_007317.3: c.146G>A, p.Arg49Gln) in 3 patients from 3 unrelated families. The clinical features appeared similar to those of patients carrying heterozygous KIF22. The homozygous KIF22 variant c.146G>A affected a conserved residue located in the active site and potentially destabilized ATP binding. As lepto-SEMDJL presents phenotypic overlap with chondrodysplasias with multiple dislocations, related to defective proteoglycan biosynthesis, we analyzed proteoglycan synthesis in patient skin fibroblasts and showed a significant decrease of total sulfated proteoglycan content in culture medium, similarly in patients with recessive or dominant KIF22 variants. These data identify a new recessive KIF22 pathogenic variant and link for the first time KIF22 pathogenic variants to altered proteoglycan biosynthesis.

Clinical spectrum of rare bone fragility disorders and response to bisphosphonate treatment: a retrospective study.

Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous group of diseases characterized by brittle bones. Though genetic mutations in COL1A1 and COL1A2 account for approximately 85-90% of OI cases, there are now more than twenty genes described, responsible for rare forms of OI. Treatment is based on the use of bisphosphonates and though it is well established that they increase lumbar spine (LS) bone mineral density (BMD), the clinical impact on fracture reduction is still debated.In this study, we investigated the clinical characteristics of 38 patients with a bone fragility disorder that had variants in non-COL1A1/COL1A2 genes in order to study genotype-phenotype correlations, as the natural history of these rare forms is still not well known. We then studied the usefulness of bisphosphonate treatment by evaluating the effects on LS BMD, annual non-vertebral fracture rate, bone turnover markers and height. This study enabled us to better define the natural history of patients with non-COL1 pathogenic variants. Patients with CRTAP and TMEM38B variants consistently had a prenatal presentation with a short (<3rd p) and bowed femur. Importantly, this prenatal involvement does not predict the postnatal severity of the disease. Regarding treatment by bisphosphonates, all patients showed a significant increase in LS BMD while treated and this increase was dependent on the dose received. The increase in LS BMD also translated in a reduction of fracture rate during treatment. Finally, our study showed that the earlier bisphosphonates are initiated, the greater the fracture rate is reduced.

European Achondroplasia Forum Practical Considerations for Following Adults with Achondroplasia.

Achondroplasia is a lifelong condition requiring lifelong management. There is consensus that infants and children with achondroplasia should be managed by a multidisciplinary team experienced in the condition. However, many people are lost to follow-up after the transition from paediatric to adult care, and there is no standardised approach for management in adults, despite the recent availability of international consensus guidelines. To address this, the European Achondroplasia Forum has developed a patient-held checklist to support adults with achondroplasia in managing their health. The checklist highlights key symptoms of spinal stenosis and obstructive sleep apnoea, both among the most frequent and potentially severe medical complications in adults with achondroplasia. The checklist acts as a framework to support individuals and their primary care provider in completing a routine review. General advice on issues such as blood pressure, pain, hearing, weight, adaptive aids, and psychosocial aspects are also included. The checklist provides key symptoms to be aware of, in addition to action points so that people can approach their primary care provider and be directed to the appropriate specialist, if needed. Additionally, the European Achondroplasia Forum offers some ideas on implementing the checklist during the transition from paediatric to adult care, thus ensuring the existing multidisciplinary team model in place during childhood can support in engaging individuals and empowering them to take responsibility for their own care as they move into adulthood.

Radiographic evaluation of ulnar deformity in patients with hereditary multiple osteochondroma and its relationship with radial head dislocation.

INTRODUCTION: In patients who have hereditary multiple osteochondroma (HMO), progressive deformity of the forearm skeleton may lead to radial head dislocation. The latter is permanent, painful and causes weakness. HYPOTHESIS: There is a relationship between the amount of ulnar deformity and the presence of radial head dislocation in patients with HMO. MATERIALS AND METHODS: This was a cross-sectional radiographic study comprising an analysis of anterior-posterior (AP) and lateral x-rays of 110 forearms in children having a mean age of 8 years and 4 months who were followed for HMO between 1961 and 2014. Four factors reflecting on the ulnar deformity in the coronal plane were investigated on the AP view and three factors in the sagittal plane were investigated on the lateral view to identify any relationship between ulnar deformity and radial head dislocation. The forearms were separated into two groups: with radial head dislocation (26 cases) and without radial head dislocation (84 cases). RESULTS: Ulnar bowing, intramedullary angle of ulnar bowing, tangent ulnar angle and overall ulnar angle were significantly higher in the group of children who had a radial head dislocation (0.05 vs 0.03, p<.001; 161 vs 167, p<001; 156 vs 162, p<001; 50 vs 30, p<.001) in univariate and multivariate analyses. DISCUSSION: Ulnar deformity, evaluated using the method described here, is more often associated with radial head dislocation than other previously published radiological parameters. This provides new insight on this phenomenon and may help to determine which factors are associated with radial head dislocation and how to prevent it. CONCLUSION: Ulnar bowing in the context of HMO, especially when evaluated on AP radiographs, is significantly associated with radial head dislocation. LEVEL OF EVIDENCE: III; case-control study.

'In-Out-In' K-wires sliding in severe tibial deformities of osteogenesis imperfecta: a technical note.

Severe infant osteogenesis imperfecta requires osteosynthesis. Intramedullary tibia's osteosynthesis is a technical challenge given the deformity and the medullar canal's narrowness. We describe an extramedullary technique: 'In-Out-In' K-wires sliding. We performed an anteromedial diaphysis approach. The periosteum was released while preserving its posterior vascular attachments. To obtain a straight leg, we did numerous osteotomies as many times as necessary. K-wires ('In') were introduced into the proximal epiphysis, and the medial malleolus ('Out') bordered the cortical and ('In') reach their opposite metaphysis. K-wires were cut, curved and impacted at their respective epiphysis ends to allow a telescopic effect. All tibial fragments are strapped on K-wires, and the periosteum was sutured over it. Our inclusion criteria were children with osteogenesis imperfecta operated before 6 years old whose verticalization was impossible. Seven patients (11 tibias) are included (2006-2016) with a mean surgery's age of 3.3 ± 1.1 years old. All patients received intravenous bisphosphonates preoperatively. The follow-up was 6.1 ± 2.7 years. All patients could stand up with supports, and the flexion deformity correction was 46.7 ± 14.2°. Osteosynthesis was changed in nine tibias for the arrest of telescoping with flexion deformity recurrence and meantime first session-revision was 3.8 ± 1.7 years. At revision, K-wires overlap had decreased by 55 ± 23%. Including all surgeries, three distal K-wires migrations were observed, and the number of surgical procedures was 2.5/tibia. No growth arrest and other complications reported. 'In-Out-In' K-wires sliding can be considered in select cases where the absence of a medullary canal prevents the insertion of intramedullary rod or as a salvage or alternative procedure mode of fixation. It can perform in severe infant osteogenesis imperfecta under 6 years old with few complications and good survival time.

Orthopedic and neurosurgical care of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is due to mutations in the PHEX gene leading to unregulated production of FGF23 and uncontrollable hypophosphatemia. XLH is characterized in children by rickets, short stature, waddling gait, and leg bowing of variable morphology and severity. Phosphate supplements and oral vitamin D analogs partially or, in some cases, fully restore the limb straightness. XLH patients may also be affected by premature, complete, or partial ossification of sutures between cranial bone, which could eventually result in cranial dysmorphia, decreased intracranial volume, and secondary abnormally high intracranial pressure with a cerebral compression. Our goal is to address the criteria and the management of the skeletal complications associated with XLH, mainly orthopedic and neurosurgical care, and reflect on decision-making and follow-up complexities.

Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations.

The GALNT3 gene encodes GalNAc-T3, which prevents degradation of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Biallelic mutations in either GALNT3 or FGF23 result in hyperphosphatemic familial tumoral calcinosis or its variant, hyperostosis-hyperphosphatemia syndrome. Tumoral calcinosis is characterized by the presence of ectopic calcifications around major joints, whereas hyperostosis-hyperphosphatemia syndrome is characterized by recurrent long bone lesions with hyperostosis. Here we investigated four patients with hyperphosphatemia and clinical manifestations including tumoral calcinosis and/or hyperostosis-hyperphosphatemia syndrome to determine underlying genetic cause and delineate phenotypic heterogeneity of these disorders. Mutational analysis of FGF23 and GALNT3 in these patients revealed novel homozygous mutations in GALNT3. Although the presence of massive calcifications, cortical hyperostosis, or dental anomalies was not shared by all patients, all had persistent hyperphosphatemia. Three of the patients also had inappropriately normal 1,25-dihyroxyvitamin D [1,25(OH)(2)D] and confirmed low circulating intact FGF23 concentrations. The four novel GALNT3 mutations invariably resulted in hyperphosphatemia as a result of low intact FGF23, but other clinical manifestations were variable. Therefore, tumoral calcinosis and hyperostosis-hyperphosphatemia syndrome represent a continuous spectrum of the same disease caused by increased phosphate levels, rather than two distinct disorders.

Healthcare trajectory of children with rare bone disease attending pediatric emergency departments.

BACKGROUND: Children with rare bone diseases (RBDs), whether medically complex or not, raise multiple issues in emergency situations. The healthcare burden of children with RBD in emergency structures remains unknown. The objective of this study was to describe the place of the pediatric emergency department (PED) in the healthcare of children with RBD. METHODS: We performed a retrospective single-center cohort study at a French university hospital. We included all children under the age of 18 years with RBD who visited the PED in 2017. By cross-checking data from the hospital clinical data warehouse, we were able to trace the healthcare trajectories of the patients. The main outcome of interest was the incidence (IR) of a second healthcare visit (HCV) within 30 days of the index visit to the PED. The secondary outcomes were the IR of planned and unplanned second HCVs and the proportion of patients classified as having chronic medically complex (CMC) disease at the PED visit. RESULTS: The 141 visits to the PED were followed by 84 s HCVs, giving an IR of 0.60 [95% CI: 0.48-0.74]. These second HCVs were planned in 60 cases (IR = 0.43 [95% CI: 0.33-0.55]) and unplanned in 24 (IR = 0.17 [95% CI: 0.11-0.25]). Patients with CMC diseases accounted for 59 index visits (42%) and 43 s HCVs (51%). Multivariate analysis including CMC status as an independent variable, with adjustment for age, yielded an incidence rate ratio (IRR) of second HCVs of 1.51 [95% CI: 0.98-2.32]. The IRR of planned second HCVs was 1.20 [95% CI: 0.76-1.90] and that of unplanned second HCVs was 2.81 [95% CI: 1.20-6.58]. CONCLUSION: An index PED visit is often associated with further HCVs in patients with RBD. The IRR of unplanned second HCVs was high, highlighting the major burden of HCVs for patients with chronic and severe disease.

Development of a broad-range 16S rDNA real-time PCR for the diagnosis of septic arthritis in children.

The broad-range PCR has been successfully developed to search for fastidious, slow-growing or uncultured bacteria, and is mostly used when an empirical antibiotic treatment has already been initiated. The technique generally involves standard PCR targeting the gene coding for 16S ribosomal RNA, and includes a post-PCR visualisation step on agarose gel which is a potential source of cross-over contamination. In addition, interpretation of the presence of amplified products on gels can be difficult. We then developed a new SYBR Green-based, universal real-time PCR assay targeting the gene coding for 16S ribosomal RNA, coupled with sequencing of amplified products. The real-time PCR assay was evaluated on 94 articular fluid samples collected from children hospitalised for suspicion of septic arthritis, as compared to the results obtained with bacterial cultures and conventional broad-range PCR. DNA extraction was performed with the automated MagNa Pure system. We could detect DNA from various bacterial pathogens including fastidious bacteria (Kingella kingae, Streptococcus pneumoniae, Streptococcus pyogenes, Salmonella spp, Staphylococcus aureus) from 23% of cases of septic arthritis giving negative culture results. The real-time technique was easier to interpret and allowed to detect four more cases than conventional PCR. PCR based molecular techniques appear to be essential to perform in case of suspicion of septic arthritis, provided the increase of the diagnosed bacterial etiologies. Real-time PCR technique is a sensitive and reliable technique, which can replace conventional PCR for clinical specimens with negative bacterial culture.

[When to think of a constructional bone disease?]. / Quand penser à une maladie osseuse constitutionnelle ?

When to think of a constitutional bone disease?. Constitutional bone diseases are a heterogenous group of disorders, variably causing: growth anomalies, joint limitation and/or hypermobility, pain, bone frailty and/or dysmorphic elements in the craniofacial sphere and the extremities. Clinical examination, radiographies with a phosphocalcic test allow to guide the diagnosis. Medical therapy for these pathologies is most of the time symptomatic, combining painkillers, kinesitherapy, and functional and/or surgical orthopedic treatment. Genetic consultation is essential to confirm the diagnosis, possibly suggest the adequate molecular analysis, discuss the genetic counselling and suggest an outline of medical therapy.

Quand penser à une maladie osseuse constitutionnelle ?. Les maladies osseuses constitutionnelles constituent un groupe hétérogène d'affections entraînant de façon variable : une anomalie de croissance, des déformations osseuses, des limitations et/ou une hypermobilité articulaire, des douleurs, une fragilité osseuse et/ou des éléments dysmorphiques de la sphère cranio- faciale et des extrémités. L'examen clinique, les radiographies avec le bilan phosphocalcique permettent d'orienter le diagnostic. La prise en charge de ces pathologies est le plus souvent symptomatique, conjuguant des antalgiques, de la kinésithérapie, et des prises en charge orthopédiques fonctionnelles et/ou chirurgicales. La consultation de génétique est indispensable pour affirmer le diagnostic, éventuellement proposer l'étude moléculaire adéquate, parler du conseil génétique et proposer les grandes lignes de prise en charge.

[Bone and joint infections in children] / Infections ostéo-articulaires de l'enfant

Bone and joint infections in children. Bone and joint infections in children are diagnostic and therapeutic emergencies. The most frequently isolated bacteria are Staphylococcus aureus and Kingella kingae. The latter gives few clinical symptoms with slightly abnormal biological signs. Improved bacteriological sampling techniques and analysis (PCR) have allowed to isolate fragile germs. The clinical examination is fundamental completed by bone scintigraphy and MRI for early diagnosis. Actual shorter antibiotic treatment protocols are currently used and shorten the duration of hospitalization. Surgical treatment with the evacuation of a collection and/ or washing of a joint is still a key point in the management of such infections. Currently, severe forms of bone and joint infections have appeared due to staphyloccocus aureus resistant to methicillin.

Infections ostéoarticulaires de l'enfant. Les infections ostéo-articulaires de l'enfant sont des urgences diagnostiques et thérapeutiques. Les germes les plus souvent isolés sont Staphylococcus aureus et Kingella kinga. Ce dernier donne un tableau clinique pauvre avec un bilan peu perturbé. L'amélioration des techniques de prélèvements bactériologiques et d'analyse (PCR) a permis d'isoler des germes fragiles. L'examen clinique est l'élément fondamental de diagnostic accompagné de l'imagerie avec la scintigraphie et l'IRM permettant un diagnostic précoce. Les nouveaux protocoles d'antibiothérapie plus courts permettent actuellement de raccourcir la durée d'hospitalisation et le traitement chirurgical avec l'évacuation d'une collection, le lavage d'une articulation, garde toujours sa place dans la prise en charge. Actuellement, des formes graves d'infections ostéoarticulaires en rapport avec des staphylocoques dorés communautaires résistants à la méticilline sont apparues.