Congenital myopathy as a new phenotype caused by two undescribed variants in ASCC1 gene.

We present a patient with congenital myopathy and an inborn epiphysiolysis of the ulna. Whole-exome sequencing analysis revealed two novel mutations in Activation Signal Cointegrator Complex 1 (ASCC1) gene in a compound heterozygous state-a splicing variant c.395-2A>G and a deletion of the first two coding exons. Homozygous and compound heterozygous LoF variants in ASCC1 gene lead to a severe phenotype of spinal muscular atrophy with congenital bone fractures 2 (SMABF2). All patients described to date presented with a severe muscular hypotony, inborn fractures, and passed away shortly after birth while our proband had moderate hypotony, no fractures, but epiphysiolysis and he was 3.5 years old at the time of examination. To explain the phenotype of our patient, we performed an RNA analysis of all family members. We discovered that the c.395-2A>G variant results in two aberrant mRNA isoforms. We also validated the deletion of two exons in ASCC1 gene that lead to the increased expression of this truncated transcript by 1.8 times. To investigate the possible impact of this deletion on the phenotype we predicted a new Kozak sequence in exon 4 that could lead to the formation of a truncated protein with shortened KH domain and a full RNA ligase-like domain. We suggest that this unexpectedly different phenotype of the proband with ASCC1-related disorder could be explained by the presence of the truncated protein with an increased expression.

Proximal femoral head transcriptome reveals novel candidate genes related to epiphysiolysis in broiler chickens.

BACKGROUND: The proximal femoral head separation (FHS) or epiphysiolysis is a prevalent disorder affecting the chicken femur epiphysis, being considered a risk factor to infection which can cause bacterial chondronecrosis with osteomyelitis in broilers. To identify the genetic mechanisms involved in epiphysiolysis, differentially expressed (DE) genes in the femur of normal and FHS-affected broilers were identified using RNA-Seq technology. Femoral growth plate (GP) samples from 35-day-old commercial male broilers were collected from 4 healthy and 4 FHS-affected broilers. Sequencing was performed using an Illumina paired-end protocol. Differentially expressed genes were obtained using the edgeR package based on the False Discovery Rate (FDR < 0.05). RESULTS: Approximately 16 million reads/sample were generated with 2 × 100 bp paired-end reads. After data quality control, approximately 12 million reads/sample were mapped to the reference chicken genome (Galgal5). A total of 12,645 genes were expressed in the femur GP. Out of those, 314 were DE between groups, being 154 upregulated and 160 downregulated in FHS-affected broilers. In the functional analyses, several biological processes (BP) were overrepresented. Among them, those related to cell adhesion, extracellular matrix (ECM), bone development, blood circulation and lipid metabolism, which are more related to chicken growth, are possibly involved with the onset of FHS. On the other hand, BP associated to apoptosis or cell death and immune response, which were also found in our study, could be related to the consequence of the FHS. CONCLUSIONS: Genes with potential role in the epiphysiolysis were identified through the femur head transcriptome analysis, providing a better understanding of the mechanisms that regulate bone development in fast-growing chickens. In this study, we highlighted the importance of cell adhesion and extracellular matrix related genes in triggering FHS. Furthermore, we have shown new insights on the involvement of lipidemia and immune response/inflammation with FHS in broilers. Understanding the changes in the GP transcriptome might support breeding strategies to address poultry robustness and to obtain more resilient broilers.

Mechanism and predisposing factors for proximal tibial epiphysiolysis in adolescents during sports activities.

BACKGROUND: Proximal tibial epiphysiolysis (PTE) can have debilitating consequences for young athletes. The mechanism and predisposing factors for this lesion have yet to be determined. To find a common denominator and a biomechanical explanation for PTE, we were using a retrospective analysis of 15 cases in combination with a systematic review of literature. METHODS: A retrospective review of medical charts was performed to identify all PTE between 2003 and 2012. Records were screened for patient age and gender, sports activity, mechanism of injury, and treatment protocols. Additionally, a literature review (MEDLINE/PubMed database, the Cochrane Library, online search engines) was conducted. RESULTS: Medical charts of 14 adolescents (15 Salter-Harris I and II fractures) were analyzed. The literature review revealed additional 75 fractures. The predominant mechanisms were landing from a jump, takeoff for a jump, stop and go movements, and eccentric muscle contraction with the knee in flexion. The main sports-activities implicated in these injuries were basketball. CONCLUSIONS: Landing from a jump with a decreased knee and hip flexion movement increases tensile forces on the proximal tibia epiphysis. During physiological epiphysiodesis, the growth plate displays an increased vulnerability and such increased tensile forces can lead to a growth plate failure. Neuromuscular fatigue can alter coordination and proprioceptive accuracy during landing from a vertical jump and thus perturbs sagittal shock absorption. In our opinion, trainers should instruct young athletes in techniques that help avoiding uncontrolled high impact landings. LEVEL OF EVIDENCE: Level IV.

Clinical and Radiographic Outcomes at 25-30 Years of a Hip Stem Fully Coated With Hydroxylapatite.

BACKGROUND: Little is known about the survival of total hip arthroplasty implants with bioactive coatings beyond the first 20 years. The authors aimed to report survival of a tapered hip stem fully coated with hydroxylapatite (HA) at follow-up of 25-30 years. METHODS: Of the original series of 320 patients (347 hips), 12 patients (12 hips) had stem and cup revisions, 54 patients (55 hips) had cup revisions, 17 patients (17 hips) had liner exchange. A total of 207 patients (225 hips) died with stems in place and 21 patients (24 hips) could not be reached. This left a cohort of 80 patients (86 hips) with their original stem for assessment. Survival was analyzed using the Kaplan-Meier (KM) method and cumulative incidence function (CIF). RESULTS: Considering stem revision as endpoint, the revision risk calculated using the KM method was 6.3%, whereas using the CIF it was 3.7%. Considering any reoperation as endpoint, the revision risk calculated using the KM method was 41.2%, whereas using the CIF it was 25.9%. The Harris Hip Score for 77 patients (18 hips) was 81.6 ± 15.2. Standard x-rays were available for 52 hips (49 patients), and 10 (19.2%) showed radiolucencies <2 mm thick. CONCLUSION: This study is the first to report outcomes of an HA-coated stem beyond 25 years. The survival of stem compares favorably with long-term survival of the Charnley cemented stem, and with shorter-term registry studies. The stem achieved its intended purpose of total osteointegration in the long-term, although the proximolateral region remains susceptible to radiolucencies.

Slipped Capital Femoral Epiphysis: Diagnosis and Management.

Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescents, occurring in 10.8 per 100,000 children. SCFE usually occurs in those eight to 15 years of age and is one of the most commonly missed diagnoses in children. SCFE is classified as stable or unstable based on the stability of the physis. It is associated with obesity, growth spurts, and (occasionally) endocrine abnormalities such as hypothyroidism, growth hormone supplementation, hypogonadism, and panhypopituitarism. Patients with SCFE usually present with limping and poorly localized pain in the hip, groin, thigh, or knee. Diagnosis is confirmed by bilateral hip radiography, which should include anteroposterior and frog-leg views in patients with stable SCFE, and anteroposterior and cross-table lateral views in unstable SCFE. The goals of treatment are to prevent slip progression and avoid complications such as avascular necrosis, chondrolysis, and femoroacetabular impingement. Stable SCFE is usually treated using in situ screw fixation. Treatment of unstable SCFE also usually involves in situ fixation, but there is controversy about timing of surgery and the value of reduction. Postoperative rehabilitation of patients with SCFE may follow a five-phase protocol.

Traumatic atlantoaxial rotatory dislocation and displaced ossiculum terminale epiphysiolysis treated with a halo device: a case report.

INTRODUCTION: The horizontal synchondroses of the infant axis are biomechanical weak regions in trauma. CASE: We report the case of a 6-year-old girl who presented with delayed atlantoaxial dislocation and displaced ossiculum terminale epiphysiolysis after a fall from a tree. TREATMENT: The patient was treated with halo traction for 3 days after which a CT scan showed normal position of the C1/C2 joint, and an acceptable position of the ossiculum terminale whereafter a halo brace was applied. Because of delayed union on CT scans, the treatment was prolonged to a total of 21 weeks. RESULT: At final follow-up 26 months after halo brace removal, the patient demonstrated normal range of movement of the neck on clinical examination and radiographs of the cervical spine including lateral flexion/extension radiographs showed no sign of instability of the atlantoaxial joint. DISCUSSION: Conservative treatment with a halo device versus surgical treatment is discussed.

Is Assessment of Femoral Head Perfusion During Modified Dunn for Unstable Slipped Capital Femoral Epiphysis an Accurate Indicator of Osteonecrosis?

BACKGROUND: The modified Dunn procedure, which is an open subcapital realignment through a surgical dislocation approach, has gained popularity for the treatment of unstable slipped capital femoral epiphysis (SCFE). Intraoperative monitoring of the femoral head perfusion has been recommended as a method of predicting osteonecrosis; however, the accuracy of this assessment has not been well documented. QUESTIONS/PURPOSES: We asked (1) whether intraoperative assessment of femoral head perfusion would help identify hips at risk of developing osteonecrosis; (2) whether one of the four methods of assessment of femoral head perfusion is more accurate (highest area under the curve) at identifying hips at risk of osteonecrosis; and (3) whether specific clinical features would be associated with osteonecrosis occurrence after a modified Dunn procedure for unstable SCFE. METHODS: Between 2007 and 2014, we performed 29 modified Dunn procedures for unstable SCFE (16 boys, 11 girls; median age, 13 years; range, 8-17 years); two were lost to followup before 1 year. During this period, six patients with unstable SCFE were treated by other procedures. All patients undergoing modified Dunn underwent assessment of epiphyseal perfusion by the presence of active bleeding and/or by intracranial pressure (ICP) monitoring. In the initial five patients perfusion was recorded once, either before dissection of the retinacular flap or after fixation by one of the two methods. In the remaining 22 patients (81%), perfusion was systematically assessed before dissection of the retinacular flap and after fixation by both methods. Minimum followup was 1 year (median, 2.5 years; range, 1-8 years) because osteonecrosis typically develops within the first year after surgery. Patients were assessed for osteonecrosis by the presence of femoral head collapse at radiographs obtained every 3 months during the first year after surgery. Seven (26%) of the 27 patients developed osteonecrosis. Measures of diagnostic accuracy including sensitivity, specificity, and the area under the receiver operating curve (AUC) were estimated. Multiple variable logistic regression analyses were used to test whether the test options were better than random chance (AUC > 0.50) at differentiating between patients who did versus did not develop osteonecrosis. Nonparametric methods were used to test for a difference in AUC across the four methods. A secondary analysis was performed to identify risk factors associated with osteonecrosis. RESULTS: After adjusting for body mass index, which was found to be a confounding variable, assessment of femoral head perfusion with ICP monitoring before retinaculum dissection (adjusted AUC: 0.79; 95% confidence interval [CI], 0.58-0.99; p = 0.006), femoral head perfusion with ICP monitoring after definitive fixation (adjusted AUC: 0.82; 95% CI, 0.65-1.0; p < 0.001), bleeding before retinaculum dissection (adjusted AUC: 0.77; 95% CI, 0.58-0.96; p = 0.006), and bleeding after definitive fixation (adjusted AUC: 0.81; 95% CI, 0.63-0.99; p = 0.001) were found to be helpful at identifying osteonecrosis. We were not able to identify a specific test that had performed best because there was no difference (p = 0.8226) in AUC across the four methods. With the numbers available, we were unable to identify clinical factors predictive of osteonecrosis in our cohort. CONCLUSIONS: Assessments of femoral head blood perfusion by ICP monitoring or by the presence of active bleeding in combination with the patient's body mass index are effective at differentiating between patients who do versus do not develop osteonecrosis after a modified Dunn procedure for unstable SCFE. Additional research is needed to determine whether information gained from assessment of femoral head perfusion during surgery should be used to guide targeted treatment recommendations that may reduce the development of femoral head deformity secondary to osteonecrosis. LEVEL OF EVIDENCE: Level III, diagnostic study.

Digital Chondrolysis and Epiphysiolysis Associated With Snakebite: A Report of 2 Cases.

BACKGROUND: Here, we present 2 cases of the unusual sequelae of a venomous bite to the finger in children resulting in chondrolysis and physeal loss. There have been few isolated case reports documenting this phenomenon. Currently, there is no preventative treatment, and patients should be warned of this possible complication of envenomation. METHODS: Two patients with chondrolysis and physeal loss have been seen in our practice. RESULTS: Chondrolysis and epiphysiolysis occurred in 2 patients. One patient was treated with proximal interphalangeal joint fusion and one is being managed conservatively. CONCLUSION: The toxic action of snake venom may cause loss of the growth plate and chondrolysis in the pediatric hand. LEVEL OF EVIDENCE: Level IV.

Overuse throwing injuries in skeletally immature athletes--diagnosis, treatment, and prevention.

The number of skeletally immature athletes participating in organized sport is near an all-time high. For nearly half a century, the medical community has investigated the link between shoulder and elbow injuries with repetitive throwing. Despite substantial literature and research, several controversies still exist, including when to begin throwing breaking pitches. Furthermore, despite introduction of pitch recommendations for youth baseball, misconceptions, poor understanding of, and adherence to these guidelines persist. High-velocity and high-volume throwing and throwing while fatigued are significant risk factors for injury. Improved awareness and adherence to throwing guidelines should limit the number of injuries. Proper identification and treatment of injuries when they do occur can allow our skeletally immature athletes to safely return to overhead sports activities.

Epiphyseal separation of the proximal humerus after birth trauma.

The purpose of this study was to report a new entity of epiphyseal slipping, which is a slipping of the upper humeral epiphysis in neonates due to birth trauma, and reporting the results of their management. Eight neonates presented with pseudo-paralysis with associated shoulder swelling and pain on passive movements of the upper limb; the radiographs revealed slipping of the proximal humeral epiphyses in six cases and associated shoulder dislocations in the other 2 cases. Failed attempts of closed reduction were done for all cases; they were managed through open reduction of the slipping and relocation of the glenohumeral joint when dislocated. The deltopectoral approach was used for management, and the slipping was fixed with k-wires through the skin. A full painless range of motion of the shoulder was achieved in all patients; no limb-length discrepancy or deformity was detected and no recurrent shoulder dislocation. In the last follow-up, all radiographs showed an anatomic reduction of the epiphyses, and all the epiphyseal plates were open. All cases showed normally growing well-formed epiphyses with no evidence of a vascular necrosis or collapse. A new entity of epiphyseal slipping was reported in this study; slipping of the upper humeral epiphysis in neonates due to birth trauma whether it is associated with shoulder dislocation or not is a benign injury with excellent results with open reduction.

[Epiphysiolysis of the medial clavicle with posterior dislocation : Video article]. / Epiphysiolyse der medialen Klavikula mit posteriorer Luxation : Videobeitrag.

OBJECTIVE OF SURGERY: The goal of surgery is the anatomical reduction and stable internal fixation of an epiphysiolysis of the medial clavicle with posterior luxation in a child without harming intrathoracic structures. INDICATIONS: This case describes an acute epiphysiolysis of the medial clavicle Aitken type 0 with posterior dislocation. CONTRAINDICATIONS: Soft tissue infections within the region of the surgical access. Allergies against any materials used in the procedure. Successful closed reduction. Additional fracture of the clavicular shaft. SURGICAL TECHNIQUE: A detailed overview of the surgical technique is available through the video, which is accessible online as well as the graphic overview in this article. Longitudinal incision over the medial clavicle up to the sternoclavicular joint and preparation onto the bony structures. Display of the epiphysiolysis. Reduction of the medial clavicle. Introduction of two Kirscher wires along the longitudinal axis in the direction of the epiphysis and introduction of two sutures. Puncture of the cartilaginous epiphysis with the two sutures. Anatomical reduction of the medial clavicle and fixation by knots. With the continuous use of the sutures, fixation to the anterior periosteum and closure of the periosteum. Wound closure. FOLLOW-UP: For 6 weeks postoperative limitation of anteversion and abduction to 90°, afterwards unlimited functionality. No routine X­ray control. RESULT: After 6 months postoperative the patient is free of pain and has full range of motion. The Constant score is 97/100.

Persisting growth after prophylactic single-screw epiphysiodesis in upper femoral epiphysis.

BACKGROUND: Prophylactic fixation of the contralateral hip in cases of slipped upper femoral epiphysis is controversial. Therefore, using a single-cannulated screw has been widely accepted. However, differing reports exist on the occurrence of persisting growth after prophylactic epiphysiodesis. The aim of this retrospective study was to evaluate the presence of persisting growth of the upper femoral epiphysis after prophylactic fixation. METHODS: From 2006 until 2009, 11 children underwent prophylactic pinning using a single-cannulated 6.5-mm cancellous screw. Time to fusion, persisting growth, and overgrowing of the screw were measured on plain radiographs taken postoperatively and at least after the growth plate was fused. RESULTS: All patients except 1 (91%) showed a persisting growth of the epiphysis, and in 2 cases a hardware replacement was necessary. The mean increase of the femoral neck length was 8.2% (SEM 1.46%). Mean follow-up was 37 months (range, 12 to 49 mo). All patients had a Risser sign grade 0 at the time of surgery, and equal or less than grade 3, when the growth plate was fused. CONCLUSIONS: Despite previous reports that a prophylactic fixation using a single-cannulated cancellous screw is unproblematic and safe, we showed that in our series growth persistence was the rule and in some cases the physeal overgrowth necessitates a hardware replacement. Careful follow-up until fusion of the growth plate should be recommended.