Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome.

Mucopolysaccharidosis type I Hurler (MPSIH) is characterized by severe and progressive skeletal dysplasia that is not fully addressed by allogeneic hematopoietic stem cell transplantation (HSCT). Autologous hematopoietic stem progenitor cell-gene therapy (HSPC-GT) provides superior metabolic correction in patients with MPSIH compared with HSCT; however, its ability to affect skeletal manifestations is unknown. Eight patients with MPSIH (mean age at treatment: 1.9 years) received lentiviral-based HSPC-GT in a phase 1/2 clinical trial (NCT03488394). Clinical (growth, measures of kyphosis and genu velgum), functional (motor function, joint range of motion), and radiological [acetabular index (AI), migration percentage (MP) in hip x-rays and MRIs and spine MRI score] parameters of skeletal dysplasia were evaluated at baseline and multiple time points up to 4 years after treatment. Specific skeletal measures were retrospectively compared with an external cohort of HSCT-treated patients. At a median follow-up of 3.78 years after HSPC-GT, all patients treated with HSPC-GT exhibited longitudinal growth within WHO reference ranges and a median height gain greater than that observed in patients treated with HSCT after 3-year follow-up. Patients receiving HSPC-GT experienced complete and earlier normalization of joint mobility compared with patients treated with HSCT. Mean AI and MP showed progressive decreases after HSPC-GT, suggesting a reduction in acetabular dysplasia. Typical spine alterations measured through a spine MRI score stabilized after HSPC-GT. Clinical, functional, and radiological measures suggested an early beneficial effect of HSPC-GT on MPSIH-typical skeletal features. Longer follow-up is needed to draw definitive conclusions on HSPC-GT's impact on MPSIH skeletal dysplasia.

Resection of Calcaneonavicular and Talocalcaneal Coalitions With Surgical Correction of the Hindfoot Valgus Deformity in One Step.

Background: Calcaneonavicular (CNC) and talocalcaneal (TCC) coalitions are the most common cause of rigid flatfoot in children. After resection, correction of the most frequent valgus-hindfoot deformity usually requires a second-step surgery. We report results of a retrospective study of patients treated with a one-step correction. Methods: Between 2008 and 2019, data were collected on 26 patients (19 male, 7 female) affected by CNC (n = 18) and TCC (n = 13), all with rigid symptomatic flatfeet. Average age at surgery was 12.5 ± 1.1 (SD) years (range, 9.8-15.2). All patients (26/26) underwent resection, 20 of 26 underwent at the same time subtalar extraarticular screw arthroereisis (SESA) for correction of residual hindfoot valgus deformity. Pre- and postoperative talocalcaneal angle according to Costa Bartani and Talar inclination angle in weightbearing were measured. Twenty-five of 26 patients had postoperative American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score. Results: Pre- and postoperative talocalcaneal average angle for CNC was respectively 141.5 ± 7.7 degrees and 130.5 ± 5.2 degrees (P < .0001) and 143.7 ± 7.7 degrees and 129.7 ± 7.0 degrees (P < .0001) for TCC. Talar inclination average angle for CNC was 29.2 ± 5.3 degrees and 19.3 ± 1.6 degrees (P < .0001) and 31.2 ± 6.4 degrees and 21.4 ± 3.4 degrees (P < .0001) for TCC. Average follow-up (FU) was 4.7 ± 3.0 years (range, 6 months-11.9 years, median 4.9 years), with a mean age at FU of 17.2 ± 5.8 (SD) years (min 12.1, max 25.3, median 16.8 years). The mean AOFAS ankle-hindfoot score for CNC and for TCC was 96.6 (range 83-100) for resection and valgus correction as one-step procedure with no statistical difference (P = .5) between CNC and TCC. No patients had additional surgery for complications or recurrence. Conclusion: Symptomatic rigid flatfeet affected by CNC and TCC treated with coalition resection and minimally invasive subtalar arthroereisis (SESA) for residual hindfoot valgus correction in one step in adolescent age achieved good to excellent results in all cases. Further surgery to correct malalignment was avoided. Level of Evidence: Level IV, retrospective study.

Transinguinal Ultrasound versus Magnetic Resonance in Spica Cast after Closed Reduction of Unstable Hips in DDH.

BACKGROUND: During the treatment of unstable hips in developmental hip dysplasia (DDH), the position of the femoral head must be assessed in spica cast (SC) after reduction. A transinguinal sonographic technique (TIT) to the hip joint has been previously described in the literature. The aim of this study is to evaluate the agreement among TIT and MR to identify hip reduction. METHODS: From 2016 to 2019, 14 consecutive newborns (10 female, 4 males) with a mean age of 2.97 ± 1.29 months were treated with closed reduction in SC. A total of 4/14 children had bilateral unstable DDH. Out of 18 hips, there were 8 hips type IV and 10 hips type IIIA, according to Graf. SC were changed monthly and hips were checked both with TIT and MR, looking for persistent dislocation. RESULTS: Overall, a mean of 2.61 SC/hip (mode = 3) was accomplished, accounting for 47 procedures, with 46 reduced hips and 1 dislocated hip: TIT and MR always agreed on the same result (47/47; Cohen k = 1, CI95 1.00 to 1.00). CONCLUSIONS: The inguinal ultrasound technique described by van Douveren showed perfect agreement with MR and might be considered a reliable alternative to check the position of the femoral head during the conservative treatment of hip dysplasia in spica cast.

Unveiling dysplasia epiphysealis hemimelica (Trevor's disease) in the foot and ankle: A systematic review.

Background: Dysplasia epiphysealis hemimelica is a rare non-inherited condition characterized by the unilateral predominance of osteochondromas in one or more epiphyses, with ankles and knees being the most affected joints. Treatment approaches vary based on the localization of the disease, encompassing both conservative and surgical options. Due to its rarity, there is a lack of definitive surgical guidelines or specific treatment modalities. Therefore, the objective of this systematic review was to thoroughly investigate dysplasia epiphysealis hemimelica to provide evidence-based guidance for managing this condition, specifically focusing on the foot and ankle. Methods: A systematic search was performed on PubMed and the Cochrane Library to identify all published articles related to dysplasia epiphysealis hemimelica of the foot and ankle. Individual patient information, such as gender, age, disease type, follow-up, localization, clinical presentation, intervention, and complications, were systematically extracted from each article and analyzed. Results: Twenty-five eligible publications were included in the review, involving a total of 70 patients (16 females, 53 males). The mean age was 9.6 years (SD 7.3). The talus was the most prevalent location and clinical presentations included mass and pain in 54% of cases. Surgical procedures were chosen in 92% of patients, with 95% undergoing mass excision. Recurrence was the most frequent complication, observed in 9% of cases. Conclusions: Raising awareness about dysplasia epiphysealis hemimelica is crucial for early diagnosis and treatment, positively impacting clinical outcomes. Vigilant monitoring is essential during observational management, as unchecked mass growth can complicate surgical intervention. Surgical treatment focuses on mass excision, feasible even at a young age but requiring precision to prevent recurrence or secondary arthritis. Level of evidence: IV.

Guided Growth in Leg Length Discrepancy in Beckwith-Wiedemann Syndrome: A Consecutive Case Series.

Beckwith-Wiedemann Syndrome (BWS) is a rare genetic disorder characterized by overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, predisposition to embryonal tumor, lateralized overgrowth, and leg length discrepancy (LLD), which can affect normal posture and gait. Aim of this study was to evaluate the effects of guided growth (temporary epiphysiodesis technique) as LLD management in BWS patients. Between 2007 and 2021, 22 BWS patients (15 F, 7 M) with a mean age of 7.9 years (2.9-14.4) and a mean LLD at first surgery of 3.65 cm (2-10), underwent temporary proximal tibial (PTE) and distal femur epiphysiodesis (DFE). In 18 patients the first surgical procedure was PTE, in one, DFE, and in 3 cases, PTE and DFE at the same time, respectively. Eleven patients reached equality of leg length after a mean follow-up of 7.7 years (3.7-13.0) and mean age of 13.3 years (12.7-27.5); 10 patients underwent 3 surgical procedures, one 7 procedures. Fifteen patients had no complications. No severe complications, infection, articular stiffness, or neuro-vascular lesions occurred in remaining patients; complications included secondary varus or valgus axial deviation in a total of 6 patients, and two screw breakages in two patients. Guided growth as a minimally invasive procedure seems efficient for LLD treatment with low complication rate in BWS patients.

Subtalar Arthroereisis for Surgical Treatment of Flexible Flatfoot.

Various surgical techniques are known for the treatment of flexible flatfoot in children after failure of nonsurgical attempts. Data collected in a review of the last 10-year period (2010-2020) show that among the 691 feet undergoing subtalar arthroereisis with endorthesis, average age at surgery was 11.40 years and in the 1856 feet that underwent subtalar arthroereisis with calcaneo-stop 11.69 years, while the complications rate was 9.00% and 6.38%, respectively. These data confirm that subtalar arthroereisis with calcaneo-stop may have an advantage over subtalar arthroereisis with endorthesis as the screw is not placed across the subtalar joint but instead into the calcaneus.

Surgical Treatment of Calcaneonavicular and Talocalcaneal Coalitions.

Tarsal coalition is determined by an absence of segmentation between one or more foot bones. The main symptom is activity-related foot pain, usually dorsolateral for calcaneonavicular coalitions and medial for talocalcaneal ones. At presentation, a symptomatic tarsal coalition must be treated conservatively for at least 6 months. If the conservative treatment fails and the foot is still painful, resection is the treatment of choice. Advantage of surgery is to restore mobility and reduce the risk of subsequent degenerative arthritis. Common pitfalls of surgery include failure to recognize associated coalitions, inadequate or extensive resection, and injury of adjoining bones.

Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome.

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is the standard of care for Hurler syndrome (mucopolysaccharidosis type I, Hurler variant [MPSIH]). However, this treatment is only partially curative and is associated with complications. METHODS: We are conducting an ongoing study involving eight children with MPSIH. At enrollment, the children lacked a suitable allogeneic donor and had a Developmental Quotient or Intelligence Quotient score above 70 (i.e., none had moderate or severe cognitive impairment). The children received autologous hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with an α-L-iduronidase (IDUA)-encoding lentiviral vector after myeloablative conditioning. Safety and correction of blood IDUA activity up to supraphysiologic levels were the primary end points. Clearance of lysosomal storage material as well as skeletal and neurophysiological development were assessed as secondary and exploratory end points. The planned duration of the study is 5 years. RESULTS: We now report interim results. The children's mean (±SD) age at the time of HSPC gene therapy was 1.9±0.5 years. At a median follow-up of 2.10 years, the procedure had a safety profile similar to that known for autologous hematopoietic stem-cell transplantation. All the patients showed prompt and sustained engraftment of gene-corrected cells and had supraphysiologic blood IDUA activity within a month, which was maintained up to the latest follow-up. Urinary glycosaminoglycan (GAG) excretion decreased steeply, reaching normal levels at 12 months in four of five patients who could be evaluated. Previously undetectable levels of IDUA activity in the cerebrospinal fluid became detectable after gene therapy and were associated with local clearance of GAGs. Patients showed stable cognitive performance, stable motor skills corresponding to continued motor development, improved or stable findings on magnetic resonance imaging of the brain and spine, reduced joint stiffness, and normal growth in line with World Health Organization growth charts. CONCLUSIONS: The delivery of HSPC gene therapy in patients with MPSIH resulted in extensive metabolic correction in peripheral tissues and the central nervous system. (Funded by Fondazione Telethon and others; ClinicalTrials.gov number, NCT03488394; EudraCT number, 2017-002430-23.).

Foot Macrodactyly Associated with Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome is a rare congenital malformation which may be associated with macrodactyly. The main problem is the need for custom-made shoes. We describe the case of a female newborn affected by Klippel-Trenaunay syndrome, with a larger and longer right foot; the difference increased progressively and, at 5 years of age, the right foot was 50% larger and 38% longer than the left one. Due to the progression of the deformity, reduction surgery was advised to reduce the foot's width. Resection of the second ray and 2nd cuneiform was performed. The result was excellent and there were no complications during a 10-year follow-up period with a decrease of width and length difference to 10% and 4%, respectively, in comparison to the contralateral foot. There were no gait anomalies. Abnormal foot width and length represented the main problems and guided the surgical strategy. Second ray resection was effective, without complications and with a good long-term functional outcome. Possibility of wearing fashionable conventional shoes without insoles was achieved to the patient's satisfaction.

Developmental dysplasia of the hip screening during the lockdown for COVID-19: experience from Northern Italy.

PURPOSE: Developmental dysplasia of the hip (DDH) ultrasound screening (USS), which is usually performed in Italy as an outpatient, was halted for an indefinite period in most centres during lockdown. The aim of this study was to analyze the effect of COVID-19 on DDH-USS, in two paediatric orthopaedic centres in one of the most critical areas of the western World. METHODS: An academic teaching hospital and paediatric trauma centre (T) and a University hospital and DDH referral centre (H), classified as national COVID-19 hubs, were involved. Graf's method was applied in both centres. In T, paediatricians directly referred only patients with delayed DDH-USS or suspicious unstable hips; in H, paediatricians or parents could directly refer to the screening service. RESULTS: The mean age of the 95 patients (190 hips) who were referred for DDH-USS in T, was 3.85 months (0.1 to 7.4); 175 were type I, nine were type IIa (+ and -), five type D and one type IV. In H, the screened patients in 2020 were only 78% of the same period in 2019. A total of 28 patients with 32 hips (8 IIb, 5 IIc, 8 D, 11 III) had late diagnosis at a mean age of 114 days (96 to 146). In the same period in 2019 only eight patients with 11 hips (8 IIb, 1 D, 1 III, 1 IV) at a mean age of 142 days (92 to 305) had late diagnosis. CONCLUSION: DDH-USS was the only screening in newborns which halted during lockdown. Few centres, which still performed diagnosis and treatment, were overloaded causing a delay in DDH management. LEVEL OF EVIDENCE: IV.

Surgical Treatment of Clubfoot in Children with Moebius Syndrome.

Moebius syndrome (MS) is a rare disease, with paralysis of the VI and VII cranial nerves, frequently associated with clubfoot (CF). The aim of this study was to evaluate surgical treatment of CF in MS, providing its peculiarities. Between 1990 and 2019, we collected data of 11 MS patients with unilateral (n = 5) or bilateral (n = 6) CF, for a total of 17 feet (9R,8L). Six patients (3M,3F) for a total of 10 feet (6R,4L) were treated elsewhere, performing first surgery at an average age of nine months, and in our hospital for relapse surgery at an average age of 4.5 years (Group 1). Five patients (3M, 2F), for a total of seven feet (3R,4L), were primarily treated in our hospital with a peritalar release according to McKay at an average age of 9.4 months (Group 2). Diméglio score was used to assess CF severity. Three questionnaires were submitted for evaluation of subjective and functional results: American Orthopedics Foot and Ankle Society for Hindfoot (AOFAS), Foot and Ankle Outcome Score (FAOS), and Foot and Ankle Ability Measure (FAAM). Average AOFAS/FAOS/FAMM scores were 82.8, 84.8, and 82.3 for Group 1, and 93.2, 94.7, and 95.1 for Group 2 at an average follow-up of 16.9 and 13.3 years, respectively. The average Diméglio score improved from 15.5 to 4.8 in the long-term follow-up in Group 1 and from 14.6 to 3.8 in Group 2. The comparison between the groups showed better results for AOFAS, FAOS, and FAAM scores for Group 2, particularly for pain, function, and foot alignment and for the post-surgical Diméglio score. CF in MS is more severe and presented a higher relapse rate (58.8%) than idiopathic CF. Peritalar release showed no relapse and better subjective and functional results in the long-term follow-up compared to other surgical techniques.

Double Diapering Ineffectiveness in Avoiding Adduction and Extension in Newborns Hips.

Hip flexion and abduction is fundamental for developmental dysplasia of the hip (DDH) treatment. At present, double diaper treatment has been inappropriately adopted when DDH is suspected. The aim of this study was to verify whether double diapers influence a newborn's hip position. Here, we studied 50 children (23 female; 27 male; average age 62.33 ± 20.50 days; average birth weight 3230 ± 447 g) with type I hips according to Graf. At the same time of the ultrasound (US) examination, the following hip positions were measured using a manual protractor: (1) spontaneous position, supine on the outpatient bed without a diaper; (2) spontaneous position, with a double diaper; and (3) squatting position on the caretakers' side. Statistical analysis was performed with a t-test to compare between (1) the spontaneous position without a diaper and with double diapers; (2) the spontaneous position with double diapers as well as the squatting position on the caretakers' side with a diaper. The comparison between the hip position without diaper and with double diapers was statistically not significant for all measurements, i.e., right hip flexion (p < 0.33), left hip flexion (p < 0.34), and right and left hip abduction (p < 0.87). The comparison between the hip position with double diapers and on the caretakers' side was statistically significant for all measurements, i.e., right hip flexion (p < 0.001), left hip flexion (p < 0.001) and right and left hip abduction (p < 0.001). We found that the use of double diapers did not affect hip position, while the position formed on the caretaker's side shows favorable influence.

Recommendations for early diagnosis of Developmental Dysplasia of the Hip (DDH): working group intersociety consensus document.

This consensus document has been prepared by a multidisciplinary group of experts (Paediatricians, Radiologists, Paediatric Orthopaedics) and it is mainly aimed at paediatricians, hospitals and primary care providers. We provide recommendations for the early diagnosis and treatment of Developmental Dysplasia of the Hip (DDH) and indications on its management.

Reduced PD-1 expression on circulating follicular and conventional FOXP3+ Treg cells in children with new onset type 1 diabetes and autoantibody-positive at-risk children.

Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and conventional (CXCR5-) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood follicular and conventional Treg cells were higher in frequency in children with new onset T1D, but expressed reduced amounts of PD-1 as compared to AAb-negative children. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to AAb-negative controls, suggesting its potential use as a biomarker of disease progression. Follicular Treg cells were reduced in frequency in the spleens of prediabetic NOD mice as they became older and turned diabetic. Interestingly, PD-1 expression declined also on circulating follicular and conventional Treg cells in prediabetic NOD mice as they aged. Together, these findings show that the frequency of circulating follicular and conventional Treg cells and their levels of PD-1 change with disease progression in children at-risk for developing T1D and in NOD mice.

The role of the labrum in early treatment of unstable developmental dysplasia of the hip.

The objective of the paper is to analyse the role of the labrum with particular attention to its morphological changes in unstable dysplastic hips during treatment.Between January 2013 and December 2015, data were collected on 86 unstable, dysplastic hips, which were divided into type D (n = 13), type III (n = 49) and type IV (n = 24). The labrum was evaluated with ultrasound examination (US) for echogenicity and dimensions with inter-/intra-observer tests comparing the US images at diagnosis and at the end of treatment. Statistical analysis was performed.At the end of treatment of unstable, dysplastic hips, the labrum was more echogenic with a frequency of 97% and was larger with a frequency of 96%.The labrum has an active stabilizing role in unstable dysplastic hips and it undergoes a statistically significant increase of echogenicity and dimensions after treatment. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180053.

International Interdisciplinary Consensus Meeting on the Evaluation of Developmental Dysplasia of the Hip.

In September 2018, an international meeting of doctors of various disciplines, with expertise in the detection and treatment of DDH, was held in Csolyospalos, Hungary. The aim was to achieve consensus on the detection and early treatment of the condition and to develop a standardized system of teaching and training for hip ultrasound. There was strong agreement that US screening is essential. Specifically the Graf technique was selected as the technique of choice. Universal US screening was strongly favored. Screening should be carried out as soon as possible, but not later than the sixth week of age. US screening is cost-effective, does not result in overtreatment, and contributes to a reduction of long-term consequences. The essential principle of treatment is timely application of a device to achieve reduction, retention and maturation, by holding the hips in flexion, and a safe degree of abduction. It was agreed that the effectiveness of any screening policy depends on the correct scanning technique. Therefore, standardization of teaching and training of the Graf technique is mandatory. A unified teaching policy and materials should be developed for this purpose. Certification, re-certification and audit were discussed. The group, which has been formalized as the International Interdisciplinary Consensus Committee On DDH Evaluation (ICODE), will continue to meet and work towards establishing international consensus on DDH, standardizing and developing teaching and training of the Graf technique for hip US, and maintaining standards for detection and management.

Risk of ulnar nerve injury during cross-pinning in supine and prone position for supracondylar humeral fractures in children: a recent literature review.

Aim of this review article is to evaluate the percentage of ulnar nerve lesion during cross-pinning considering the patient's position (supine or prone) on the surgical bed. Comprehensive research was performed by searching in PUBMED, Cochrane Library, ISI Web of Science, SCOPUS and Clinicaltrials.gov from 2005. Children with extension type supracondylar humeral fractures without clinical signs of ulnar nerve lesion at presentation were included. A total of 28 papers were examined including 2147 patients; 1541 underwent a closed reduction and cross-pinning in supine position and 606 in prone position. Among 1541 patients in supine position, 69 (4.5%) suffered from a ulnar nerve injury while among the 606 patients treated in prone position none ulnar nerve lesions were reported. Despite the apparent safety of prone position, further larger studies, comparing the patient's position on the surgical bed, need to be carried out in order to confirm this likelihood.

Ultrasonographic changes of labrum morphology in patients with developmental dysplasia of the hip: a preliminary report on 74 dysplastic and unstable hips.

The aim of the study was to verify the labrum's morphological changes in unstable and dysplastic hips during treatment. Between January 2013 and April 2015, 74 dysplastic hips were divided into type D (n=12), type III (n=40), and type IV (n=22). The labrum was evaluated on ultrasonography (US) for echogenicity and dimensions with interobserver/intraobserver tests: test 1 (US at diagnosis and control group), test 2 (US at diagnosis and 6 weeks post-treatment), and test 3 (US at diagnosis and at end of treatment). Statistical analysis was performed. The labrum was less echogenic in test 1 and more echogenic in test 3, and the labrum was smaller in test 1 and larger in test 3. The labrum undergoes statistically significant increase of echogenicity and dimensions after treatment, suggesting a stabilizing role. Level of Evidence: Level II, Oxford Center for Evidence-based Medicine.

Advantages and disadvantages of the prone position in the surgical treatment of supracondylar humerus fractures in children. A literature review.

INTRODUCTION: Supracondylar humerus fractures are the most common elbow injuries in children. The widely adopted approach for Gartland III extension type consists of closed reduction and percutaneous pinning; the pin configuration can be lateral or crossed in relationship with the habit of the surgeons. Iatrogenic injury of the ulnar nerve is the most common risk during the insertion of the medial pin. The aim of this study was to analyze advantages and disadvantages of percutaneous pinning with the patient in prone position. MATERIALS AND METHODS: A literature review of the period 2005-2017 was carried out; four medical search engine (Pubmed, Cochrane Library, ISI Web of Science and Scopus) were consulted using the review's filter and the key words "Ulnar nerve AND supracondylar humerus fractures". The total number of patients were analyzed for: ulnar nerve injuries, anesthesiologic management, time of surgery. RESULTS: Twenty-nine papers were read, 23 regarding cross pinning in supine position and 6 in prone position. On one hand, 1529 children were treated with closed reduction and cross pinning in supine position; 69 of these patients (4.5%) suffered from iatrogenic ulnar nerve injury. On the other hand, 579 patients underwent the same treatment in prone position; no ulnar nerve lesions were reported in this group. Only one article compared both groups of children in supine and prone position regarding time of anesthesia which is slightly higher in the prone group. There were no differences between supine and prone positions regarding x-ray exposition, time of surgery, closed reduction manoeuvers, pin positioning, x-ray results, clinical and functional results. DISCUSSION AND CONCLUSIONS: The ulnar nerve in children is hypermobile in the cubital tunnel and tends to dislocate anteriorly over the medial epicondyle, especially when the elbow is in hyperflexion. This may be the reason of the increased risk of nerve injury during the insertion of the medial pin in supine position and, instead, an advantage of the prone position. The insertion of both pins from the lateral side could reduce this complication. Larger studies need to be carried out regarding the reported higher duration of anesthesia in prone position.

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.