Association Analysis of GDF5 and Contributing Factors in Developmental Dysplasia of the Hip in Infants.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a developmental disorder which is reported to be associated with hip instability. When untreated, it can lead to irreversible joint damage. DDH is known to be a multifactorial disease involving genetic, mechanical and environmental factors. The greatest causative potential is attributed to the genetic component. Growth Differentiation Factor 5 (GDF5) is among the most studied genes associated with processes of regeneration and maintenance of joints. The aim of this work was to analyse the association of SNP rs143383 in the GDF5 gene and the occurrence of DDH, along with association with various contributing factors in the Caucasian population. MATERIAL AND METHODS: A total of 118 samples were analysed for the presence of the mutation. DNA was isolated from all individuals from peripheral blood. SNP rs143383 in the GDF5 gene was genotyped using the TaqMan assay. A standard chi-square test was used to compare allele and genotype distributions in patients and healthy controls. RESULTS: The association analysis of genotypes of DDH and rs143383 revealed a significant association. Also, the association of GDF5 and selected contributing factors was statistically significant in female gender (p=0.002), family history (p<0.001), count of pregnancy (p=0.009), laterality of hip involvement and initial US examination. CONCLUSIONS: 1. The results indicate an important effect of rs143383 polymorphism in the GDF5 gene on DDH development. 2. However, our results also suggest that rs143383 is not the only contributing factor in the genetic component of DDH.

Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is one of the most prevalent skeletal disorders. DDH is considered a pathologic condition with polygenic background, but environmental and mechanic factors significantly contribute to its multifactorial etiology. Inheritance consistent with autosomal dominant type has also been observed. Single-nucleotide polymorphisms (SNPs) in various genes mostly related to formation of connective tissue are studied for a possible association with DDH. METHODS: We genotyped three SNPs, rs1800796 located in the promoter region of the IL6 gene, rs143383 located in the 5' untranslated region (UTR) of the GDF5 gene and rs726252 located in the fifth intron of the PAPPA2 gene. The study consisted of 45 subjects with DDH and 85 controls from all regions of Slovakia. RESULTS: Association between DDH occurrence and studied genotypes affected by aforementioned polymorphisms was confirmed in the case of rs143383 in the GDF5 gene (p = 0.047), where the T allele was over-expressed in the study group. Meanwhile, in the matter of IL6 and PAPPA2, we found no association with DDH (p = 0.363 and p = 0.478, respectively). CONCLUSIONS: These results suggest that there is an association between DDH and GDF5 polymorphisms and that the T allele is more frequently presents in patients suffering from DDH.

Genetics of developmental dysplasia of the hip.

In the last decade, the advances in the molecular analyses and sequencing techniques allowed researchers to study developmental dysplasia of the hip (DDH) more thoroughly. Certain chromosomes, genes, loci and polymorphisms are being associated with variable severity of this disorder. The wide range of signs and symptoms is dependent either on isolated or systemic manifestation. Phenotypes of isolated cases range from only a mild ligamental laxity, through subluxation, to a complete dislocation of the femoral head. Systemic manifestation is connected to various forms of skeletal dysplasia and other malformations characterized by significant genetic aberrations. To reveal the background of DDH heredity, multiple studies focused on large sample sizes with an emphasis on the correlation between genotype, phenotype and continuous clinical examination. Etiological risk factors that have been observed and documented in patients include genetic, environmental, and mechanical factors, which significantly contribute to the familial or nonfamilial occurrence and phenotypic variability of this disorder. Still, the multifactorial etiology and pathogenesis of DDH are not yet sufficiently clarified, explained, or understood. Formation of connective tissue, osteogenesis, chondrogenesis, and all other affected pathways and variations in the function of their individual elements contribute to the creation of the pathology in a developing human body. This review article presents an up-to-date list of known DDH associated genes, their products, and functional characteristics.

Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects.

As one of the most frequent skeletal anomalies, developmental dysplasia of the hip (DDH) is characterized by a considerable range of pathology, from minor laxity of ligaments in the hip joint to complete luxation. Multifactorial etiology, of which the candidate genes have been studied the most, poses a challenge in understanding this disorder. Candidate gene association studies (CGASs) along with genome-wide association studies (GWASs) and genome-wide linkage analyses (GWLAs) have found numerous genes and loci with susceptible DDH association. Studies put major importance on candidate genes associated with the formation of connective tissue (COL1A1), osteogenesis (PAPPA2, GDF5), chondrogenesis (UQCC1, ASPN) and cell growth, proliferation and differentiation (TGFB1). Recent studies show that epigenetic factors, such as DNA methylation affect gene expression and therefore could play an important role in DDH pathogenesis. This paper reviews all existing risk factors affecting DDH incidence, along with candidate genes associated with genetic or epigenetic etiology of DDH in various studies.

Developmental Dysplasia of Hip: Perspectives in Genetic Screening.

Development dysplasia of the hip (DDH) is a complex developmental disorder despite being a relatively common condition mainly caused by incompatibility of the femoral head and the abnormal joint socket. Development dysplasia of the hip describes a wide spectrum of disorders ranging from minor acetabular dysplasia to irreducible dislocation of the hip. Modern medicine still suffers from lack of information about screening and precise genetic examination. Genome wide linkage and association studies have brought significant progress to DDH diagnosis. Association studies managed to identify many candidate (susceptible) genes, such as PAPPA2, COL2A1, HOXD9, GDF-5, and TGFB1, which play a considerable role in the pathogenesis of DDH. Early detection of DDH has a big chance to help in preventing further disability and improve the psychological health and quality of life in those children. This emphasizes the importance to establish a universal screening program along with the genetic counseling.

Identification of Prognostic and Predictive Osteosarcoma Biomarkers.

Both adolescents and children suffer from osteosarcoma, localized in the metaphysis of the long bones. This is the most common primary high-grade bone tumor in this patient group. Early tumor detection is the key to ensuring effective treatment. Improved osteosarcoma outcomes in clinical trials have been contingent on biomarker discovery and an evolving understanding of molecules and their complex interactions. In this review, we present a short overview of biomarkers for osteosarcoma, and highlight advances in osteosarcoma-related biomarker research. Many studies show that several biomarkers undergo critical changes with osteosarcoma progression. Growing knowledge about osteosarcoma-related markers is expected to positively impact the development of therapeutics for osteosarcoma, and ultimately of clinical care. It has also become important to develop new biomarkers, which can identify vulnerable patients who should be treated with more intensive and aggressive therapy after diagnosis.

Congenital insensitivity to pain in one family.

Congenital insensitivity to pain (CIP) is a rare autosomal recessive genetic disease caused by mutation in several different genes. The diagnosis requires the combined skills and cooperation of pediatricians, neurologists, radiologists, pathologists, and orthopedic surgeons. Orthopedic manifestations of CIP include delayed diagnosis of fractures, nonunions, Charcot arthropathy, avascular necrosis, osteomyelitis, joint dislocations, and heterotopic ossifications. We present case reports of two brothers with CIP with various orthopedic manifestations and methods of surgical treatment with 10 years of follow-up.

Carpal Tunnel Syndrome: Symptoms, Causes and Treatment Options. Literature Reviev.

Carpal Tunnel Syndrome (CTS) is the most common form of entrapment neuropathy. Several authors have investigated the anatomical and pathophysiological features of CTS and have identified several parameters that, in combination, play a significant role in its pathophysiology. Advancement in biological research on CTS has enabled the advent of efficient diagnostic techniques such as provocative tests and nerve conduction studies. Sophisticated technologies, such as magnetic resonance imaging (MRI) and ultrasonography (US), have facilitated the diagnosis of CTS. This review article aims at consolidating the relevant medical literature pertaining to the symptoms, pathophysiology, clinical diagnosis and treatment strategies of CTS. It also compares the various methods of diagnosis and discusses their benefits and disadvantages. Finally, it sheds light on the conservative vs. surgical approach to treatment and compares them. While the surgical approach has proved to be more efficient relative to the conservative methods of steroid injections and splinting, many studies have demonstrated both advantages and adverse effects of the surgical methods. Surgical options and complications are discussed in detail. This article comprehensively summarizes all medical aspects of CTS to update medical professionals' knowledge regarding the disease.

Infection in Bone Allograft Transplants.

Bone allografts are widely being used in clinical practice for bone reconstruction. They are considered to be the most preferred alternative to bone autografts, mainly due to their availability and the elimination of donor site morbidity. The risk of bacterial and viral disease transmission, albeit low, is one of the major concerns associated with bone allograft transplant. This review focuses on the epidemiologic and microbiologic aspects of bone allograft infections and the current prevention and treatment options. It also discusses the role of the regulatory authorities in ensuring the safety and efficacy of bone allografts.

[Small cell type (Ewing-like) clear cell sarcoma of soft parts: a case report]. / Malobunecná varianta svetlobunecného sarkomu mekkých tkání napodobující Ewinguv sarkom - kazuistika.

The authors present a unique case of small cell variant of clear cell sarcoma of soft parts in a 42-year old woman. The tumor originally arose in the right flank of the soft tissues and ultimately developed both a local recurrence and multiple distant skin metastases two years and ten months thereafter. Nonspecific morphology of small blue round cell tumor was preserved at all microscopically verified sites and initially led to the spectrum of erroneous diagnoses such as an extraskeletal myxoid chondrosarcoma, Ewing sarcoma as well as malignant melanoma. The distinctive features of clear cell sarcoma such as fascicular nested growth pattern, spindling, clear cell change and/or eosinophilic cytoplasm were not disclosed even by extensive sampling. Immunohistochemically, the tumor expressed only S100protein and HMB45; all other markers (CD99, FLI1, cytokeratins, EMA) were completely negative. The molecular analysis carried out in one of the cutaneous metastases revealed translocation t(12;22) (EWSR1-ATF1) and ultimately led to the correct diagnosis of unusual Ewing-like clear cell sarcoma. Discussed is the implementation of molecular tests in routine diagnostics considering the existence of both histologically and biologically different tumors with an identical pathogenic molecular background.

Acetabular revision arthroplasty using trabecular titanium implants.

PURPOSE: The aim of this study was to evaluate early results of acetabular revisions of total hip replacement using fully cementless trabecular titanium (TT) acetabular modular implants (Delta Trabecular Titanium, Limacorporate, Udine, Italy). METHODS: Between March 2009 and May 2012 TT was used in 81 revisions. The mean age at the time of revision was 68 years (32-84 years). There were nine patients revised for type 1, 11 for type 2A, 27 for type 2B, six for type 2C, 15 for type 3A and 13 for type 3B acetabular defects according to the Paprosky classification. Frozen morselised bone allografts were used in 53 cases and bulk structural allografts in three cases. Clinical evaluations were made using a modified functional Merle d'Aubigné-Postel score. The mean follow-up period was 38.14 months (24-62 months). RESULTS: The mean pre-operative Merle d'Aubigné-Postel functional score was 4.7 and 9.8 at the time of last follow-up. There was one revision due to instability of the acetabular component. A cage system-Delta Revision TT-was successfully used in this case. Three cases with Paprosky type 3B defect showed cranial migration of the acetabular component by 6 mm, but stabilised after six months. No dislocations associated with acetabular surgery have occurred in the cohort. There have been no dissociations of the modular component. A fatigue fracture of the hemispherical module occurred in the revised case. No other hardware mechanical failures have been recorded. CONCLUSIONS: TT cups, hemispherical modules and augments facilitate reliable and reproducible biological fixation in acetabular revision surgery with excellent results. Extended follow-up is necessary to evaluate the long-term performance of TT modular implants.

Arthroscopic management of anterior instability of the shoulder.

BACKGROUND: The aim of all shoulder joint stabilization surgery is to prevent further dislocation and restore anatomical continuity of the capsule-labral complex to the anterior and inferior edge of the glenoid. In this study, the authors analyzed the results of arthroscopic stabilization techniques using the method of suture anchors in patients with recurrent anterior shoulder instability. MATERIAL AND METHODS: During the reporting period they performed surgery on 91 patients with anterior shoulder instability using the method of MITEK GII suture anchors and BIO ANCHOR . The group consisted of 19 women and 72 men with a mean age of 28.6 years (range 16-70 years). RESULTS: In the preoperative evaluation, the mean Rowe score was 37.1 (range 15-55). Postoperatively there was a significant increase (p < 0.000) in the score analysed using Rowe with a mean of 87.4 (range 45-100). When analyzing the results of operations, they evaluated the function as excellent in 65 patients (71.4 %) and 14 patients (15.4 %) were evaluated as good function. A satisfactory function was observed in 12 patients (13.2 %). For five patients, there was recurrence of instability of the shoulders. CONCLUSIONS: Arthroscopic stabilization of post-traumatic shoulder instability using the suture anchor technique is the optimal solution for anterior shoulder instability. In conjunction with comprehensive treatment and subsequent rehabilitation an early return to the preoperative activities can be achieved with a reduction of residual restriction of shoulder movement.

[Where does Ewing sarcoma end and begin - two cases of unusual bone tumors with t(20;22)(EWSR1-NFATc2) alteration]. / Kde koncí a zacíná diagnóza Ewingova sarkomu - popis dvou neobvyklých kostních nádoru s translokací t(20;22)(EWSR1-NFATc2).

The authors present two cases of Ewing-like sarcoma of the humerus and femur of a 12-year-old boy and a 28-year-old male, respectively. Identical morphology in both tumors consisted of multiple solid nests with a mosaic collection of small, round, uniform cells with clear cytoplasm and no apparent nuclear atypia. A monotonous structural arrangement, including both rich vascularity of bordering septae and significant admixtures of eosinophil leucocytes, resulted in a final organoid "neuroendocrine-like" pattern. Immunohistochemistry revealed diffuse strong CD10, CD99 and CD138 positivity. Detailed molecular analysis in both tumors confirmed translocation t(20;22) resulting in an EWSR1-NFATc2 fusion gene. Additionally, this translocation was accompanied by amplification of the proximal part of the genes and surrounding areas. Clinically, both neoplasms behaved aggressively and they were primarily chemoresistant. Four years later, the patient with the lesion in the humerus developed a massive local recurrence with a disruption of osteosynthesis. The last follow-up disclosed suspicious metastatic deposits in the lung. The boy with the femoral tumor underwent a total femoral prosthesis and there are no signs of local or systemic recurrence after 11 months of follow-up. The authors discuss the taxonomic placement of these rare examples of Ewing-like sarcoma family in the light of new molecular discoveries.

Surgical options for the treatment of simple bone cyst in children and adolescents.

BACKGROUND: There are several treatment options for simple bone cysts, with treatment depending mainly on the experience and preference of the surgeon and the extension and location of the cyst. OBJECTIVES: To assess our experience with the surgical treatment of bone cyst lesions in pediatric patients at one institution by the same group of surgeons. METHODS: The study group comprised 60 patients (43 boys, 17 girls) treated surgically for monostatic lesions between January 2002 and July 2007. The mean age at surgery was 11.8 years (range 4-17 years). Mean follow-up was 4.2 years. Most of the lesions were located at the proximal humerus. Patients were divided into five groups according to treatment method: a) corticosteroids (methylprednisolone 40-80 mg) (n = 26); b) curettage and bone grafting (fibula or iliac crest) ( n = 16); c) aspiration of the bone cavity and subsequent bone marrow transplantation ( n = 10); d) internal preventive fixation using an elastic stable intramedullary nail (n = 5); and e) curettage and implantation of a synthetic cancellous bone substitute (pure beta-tricalcium phosphate substitute, ChronO, Synthes, Switzerland) ( n = 3). RESULTS: Treatment success was evaluated by the Capanna criteria. Successful results were observed in 68% (18 complete healing, 23 healing with residual radiolucent areas), 30% recurrence rate, and no response to treatment in one patient (2%). We recorded recurrence in 50% of the children treated by corticosteroid injection, and one child did not respond to treatment. CONCLUSIONS: The best results were achieved in children treated by curettage and the subsequent use of an osteoconductive material, and in children treated with elastic intramedullary nail fixation. Despite our limited experience with calcium-triphosphate bone substitute, the treatment was mostly successful. Because of the short follow-up, further observation and evaluation are necessary.

Rare peripheral femoral nerve neuropathy in children.

Peripheral neuropathy of the femoral nerve is extremely rare. In the literature, we found descriptions of only 50 similar patients, mainly as a complication of coagulopathies, and none of intrapelvic tumors. Three children with a rare peripheral neuropathy of the femoral nerve as a complication of extraperitoneal pelvic masses are described in this report. In all three, the neuropathy was caused by stretching of the femoral nerve over a huge intrapelvic mass. None was related to coagulopathy. After removal of the masses, full recovery from the neurological symptoms was observed in two children and the recovery of the patient with Ewing's sarcoma is satisfying, at the 2-year follow-up and at the time of writing. As early surgical debulking of the mass was a good influence on the recovery of the nerve paresis, we believe that is imperative in the treatment process. Medical staff should be aware that a serious illness can lie behind peripheral femoral nerve neuropathy.

Pavlik's method: a retrospective study.

This retrospective study of the early work of Arnold Pavlik in the treatment of developmental dysplasia of the hip proves the success of his method in eradicating avascular necrosis (AVN) resulting from other modes of treatment. Authors analyzed some 100 charts of children treated for CDH, as it was known at that time, between 1969 and 1981, and assessed the influence of gender, clinical stability, severity of X-ray pathology and age at which treatment was started, according to duration, outcome of treatment and rate of AVN. Of the 100 children with 134 treated pathological hips, 62 children with 86 pathological hips were treated exclusively by Pavlik's method. Length of treatment for the 86 hips successfully treated by Pavlik's method only was an average of 6 months. No AVN was found for any hip treated by Pavlik's method only, including dislocated hips. The 65% of failure rate was for dislocated hips only. Late onset and prolonged duration of treatment using Pavlik's method contributed to relative high failure rate followed by AVN. This leads to the conclusion that Pavlik's method is safe and accurate for all dysplastic and subluxated hips, along with the vast majority of dislocated hips.

New conservative treatment of idiopathic scoliosis: effectiveness of therapy.

Background. This article provides basic information concerning a new conservative treatment for idiopathic scoliosis, with appropriate asymmetric flexion-rotation exercises and special redressing positions. Material and method. The analysis was based on 288 children with scoliosis and a control group of 268 children. The authors describe the most important exercises and provide a statistical analysis of treatment outcome in children with idiopathic scoliosis. Results and Conclusions. Early detection of the risk of scoliosis and correct therapy through new conservative treatment based on exercises make it possible not only to limit the progression of spinal deformity (61%), but also, in some cases of incipient scoliosis, to reduce the curvature (32%).

Present status of screening and prevention of developmental dysplasia of the hip in the Slovak Republic.

The authors analysed the status of screening and prevention of developmental dysplasia of the hip in the Slovak Republic on the basis of the European Pediatric Orthopaedic Society questionnaire. The questionnaire was sent to 31 heads of orthopaedic departments, with 23 (74%) responses. According to the responses received, in the Slovak Republic a neonatologist or orthopaedic surgeon, depending on availability, makes the first clinical examination of the hips up to the fifth day after delivery. Every instability, relative shortening of one of the lower limbs, or 'high-risk' baby is referred immediately to the orthopaedic surgeon. Sonographic examination up to 7 days after delivery is performed in six departments. In another 11 departments, two or more sonographic examinations are performed on each baby. Authors support the simple static ultrasound as an effective screening test for developmental dysplasia of the hip, that should be applied to the whole population and not simply to the at risk group.