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Background: This study evaluates the radiological parameters of developing subsequent contralateral slips in unilateral slipped capital femoral epiphysis (SCFE) patients at the time of initial presentation., Methods: The study group included the review of unilateral SCFE patients treated between June 2007 and August 2018. Age, gen-der, side, stability, posterior slope angle, grade of slip, modified Oxford bone age score (mOBAS), the Risser classification, and the ap-pearance of the triradiate cartilage were evaluated retrospectively. Data were analyzed between two groups: subsequent contralateral SCFE (SCFESC) patients that developed contralateral slip during follow-up and unilateral SCFE (SCFEU) patients that did not develop contralateral slip up to skeletal maturity. Descriptive statistics were used to compare risk factors between groups., Results: This study included 48 patients and 6 patients (12.5%) developed a SCFESC. Only mOBAS was significantly different be-tween groups. The mOBAS scores in SCFESC were 18 in 2 patients (33.3%), 19 in 4 patients (66.7%). The mOBAS scores in SCFEU were 18 in 1 patient (2.4%), 19 in 24 patients (57.1%), and >20 in 17 patients (40.5%). In the SCFESC group, all patients had a Risser score of 0 and all had open triradiate cartilage., Conclusion: Patients with unilateral SCFE are at risk for SCFESC, and the mOBAS is the best predictor of risk assessment. We agree that mOBAS score of 16,17 or 18 patients' contralateral hips can be prophylactically pinned. We also suggest pinning or close screening of mOBAS 19 patients that some carry relatively high risk of subsequent contralateral slip.

The Beckwith-Wiedemann spectrum (BWSp) ranges from isolated lateralized overgrowth (ILO) to classic phenotypes. In this broad clinical spectrum, an epigenetic alteration on chromosome 11p15.5 can be detected. The risk for embryonal tumors is high, especially in patients with lateralized overgrowth (LO). The aim of this study is to investigate epigenetic alterations in 11p15.5 and tumor risk in 87 children with LO. The methylation level of 11p15.5 was examined in the blood of all patients and in skin samples or buccal swabs from 40 patients with negative blood tests; 63.2% of patients were compatible with the ILO phenotype, 18.4% were atypical, and 18.4% were classic. The molecular diagnosis rate was 81.2% for the atypical and classic phenotypes, and 10.9% for the ILO phenotype. In patients with epigenetic alterations, LO was statistically significantly more severe than in test negatives. Tumors developed in six (6.9%) of the total 87 patients with LO; four belonged to the atypical or classical phenotype (12.5%) and two to ILO (3.5%). Three of the four patients with atypical/classical phenotypes had pUPD11, one had IC1-GOM alteration, and two ILO patients were negative. We conclude that LO patients should be monitored for tumor risk even if their epigenetic tests are negative.

Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic mutations in GALNS gene and characterized by progressive skeletal deformities with short stature. The aim of this study was to evaluate the genotype, longitudinal height measurement and clinical features of MPS IVA patients. Thirty-two patients from 22 families were enrolled. The ages of patients at diagnosis ranged from two months to 18 years of age, and followed up for three to twenty years. They were classified as severe and attenuated form (intermediate and mild) according to their height measurements. The mean height standard deviation scores (SDS) for Turkish standards at 0-3, 5 and 10 years of ages were found to be -1.1, -4.2 and -7.3 respectively in patients with severe phenotype, while they were +0.4, -1.5 and -3 for intermediate phenotype. Patients with severe form reached a mean final height of -8.5 SDS, and mild phenotype -3.6 SDS. The most common initial and current symptoms in the patients with the severe phenotype were pectus carinatus and/or kyphosis deformities which occurred between 5 months and 3 years of age, and genu valgum deformity which developed after 3 years of age. However, kyphoscoliosis was the most common initial and current findings in the attenuated phenotype. Although, initial symptoms appeared in early childhood in the intermediate phenotype, similar to the severe phenotype, the clinical findings progressed slowly and genu valgum deformity did not develop. In patients with mild phenotype, the onset of symptoms was after 5 years of age. In conclusion, this study provides significant insights into the initial and follow-up clinical features and height values that contribute to the differential diagnosis of the severe and intermediate phenotypes in early childhood. Eleven mutations in GALNS gene in which one of them is novel (c.416G>A) were associated with the severe phenotype and three mutations (c.1038C>A, c.850T>G, c.752G>A) lead to the attenuated phenotype., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Greater trochanter apophysiodesis (GTA) is relatively minimal invasive technique for the treatment of trochanteric overgrowth. Various types of implants can be used in each procedure. The purpose of this study was to compare outcomes of three different types of implants that were used in treatment of trochanteric overgrowth in Legg-Calve-Perthes disease., Materials and Methods: We retrospectively studied radiological results of three implants (screw, screw washer, and EP) on inhibiting trochanteric growth in 32 patients. Articulo-trochanteric and trochanter-trochanter distances (TTDs) were measured on radiographs. Embedding of implant evaluated on final radiographs., Results: The mean of age at the surgery was 10 ± 2.3 years, and the mean of follow up period was 50.0 ± 16.7 months. In all groups, articulo-trochanteric distance was decreased on final radiographs. In screw and screw washer group, increase of TTD was not statistically significant ( P < 0.05). Twelve, one, and two implants were embedded, respectively, in screw, screw washer, and EP groups. Two patients in EP group had revision surgery due to loosening., Conclusions: In this study group, GTA using screw and screw washer methods could slow down but did not restore trochanteric overgrowth. We suggest using washer to reduce embedding of the screw., Competing Interests: There are no conflicts of interest.

Aim: To compare the postoperative changes of both sagittal spinal and spinopelvic parameters in patients with Lenke Type 1 adolescent idiopathic scoliosis (AIS) who underwent selective and non-selective fusion surgery., Material and Methods: We conducted a retrospective study among 53 Lenke Type 1 AIS patients who underwent corrective surgery at our centre between 2006 and 2012. Patients were classified as group 1 if they underwent selective surgery and as group 2 if they underwent non-selective surgery. Surgical results of preoperative and postoperative sagittal and spinopelvic measurements, pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL) and thoracic kyphosis (TK) values were analysed using the SURGIMAP© Software (Nemaris İnc. USA) measurement system., Results: In both groups, a comparison of pre- and postoperative sagittal spinal parameters did not show a statistically significant difference. In both groups, pre- and postoperative measurements of LL and TK did not show a statistically significant difference., Conclusion: After selective and non-selective surgery, sagittal spinal and spinopelvic parameters are not affected in the middle term. We think that the long-term studies to be done in this regard will increasingly require the necessity of keeping the pelvis in mind while evaluating the sagittal plan in AIS surgery.

Objective: The aim of this study was to compare the treatment outcomes of mid-diaphyseal clavicular fractures between an external fixator and more widely selected treatment options such as plate osteosynthesis or conservative methods., Materials and Methods: The medical records of 64 patients who were treated for mid-diaphyseal clavicular fracture in our clinic from 2009 to 2013 were reviewed. The inclusion criterion was mid-diaphyseal closed clavicular fractures with shortening of more than 2 cm. The Constant and DASH (disabilities of the arm, shoulder, and hand) scores at the final follow-up, initial displacement, nonunion, and complication rates were compared. Statistical differences between groups were assessed with the Kruskal-Wallis test, and pairwise comparison analysis was used to evaluate the differences within the groups., Results: Of the 64 patients, 24 (37.5%) were treated with plate osteosynthesis (group 1), 11 (17.2%) with an external fixator (group 2), and 29 (45.3%) conservatively with a figure-of-eight bandage (group 3). The mean follow-up periods were as follows: group 1: 37 ± 10.4 months, group 2: 33 ± 7 months, and group 3: 35 ± 9.4 months. The initial amount of displacement and DASH score were: group 1: 89.1 ± 7.8, group 2: 89.1 ± 7.8, and group 3: 6.1 ± 6.6) (p = 0.079). The Constant score of group 2 (93 ± 6.1) was significantly higher than that of group 3 (85 ± 8.4) (p = 0.013). No statistical difference was found in the distribution of nonunions (p = 0.387). However, in group 3, the number of malunions (11/29, 37.9%) was significantly higher compared to the other 2 groups (group 1: 1/24, 4.2%; group 2: 2/11, 18.2%) (p = 0.006)., Conclusions: This study revealed that the treatment of acute clavicular fractures with an external fixator was a good alternative to plate osteosynthesis or conservative treatment., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Background: Arthrogryposis, defined as congenital joint contractures in 2 or more body areas, is a clinical sign rather than a specific disease diagnosis. To date, more than 400 different disorders have been described that present with arthrogryposis, and variants of more than 220 genes have been associated with these disorders; however, the underlying molecular etiology remains unknown in the considerable majority of these cases., Methods: We performed whole exome sequencing (WES) of 52 patients with clinical presentation of arthrogryposis from 48 different families., Results: Affected individuals from 17 families (35.4%) had variants in known arthrogryposis-associated genes, including homozygous variants of cholinergic γ nicotinic receptor (CHRNG, 6 subjects) and endothelin converting enzyme-like 1 (ECEL1, 4 subjects). Deleterious variants in candidate arthrogryposis-causing genes (fibrillin 3 [FBN3], myosin IXA [MYO9A], and pleckstrin and Sec7 domain containing 3 [PSD3]) were identified in 3 families (6.2%). Moreover, in 8 families with a homozygous mutation in an arthrogryposis-associated gene, we identified a second locus with either a homozygous or compound heterozygous variant in a candidate gene (myosin binding protein C, fast type [MYBPC2] and vacuolar protein sorting 8 [VPS8], 2 families, 4.2%) or in another disease-associated genes (6 families, 12.5%), indicating a potential mutational burden contributing to disease expression., Conclusion: In 58.3% of families, the arthrogryposis manifestation could be explained by a molecular diagnosis; however, the molecular etiology in subjects from 20 families remained unsolved by WES. Only 5 of these 20 unrelated subjects had a clinical presentation consistent with amyoplasia; a phenotype not thought to be of genetic origin. Our results indicate that increased use of genome-wide technologies will provide opportunities to better understand genetic models for diseases and molecular mechanisms of genetically heterogeneous disorders, such as arthrogryposis., Funding: This work was supported in part by US National Human Genome Research Institute (NHGRI)/National Heart, Lung, and Blood Institute (NHLBI) grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, and US National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS058529 to J.R. Lupski.

Background: Treatment of hip instability in patients with lower lumbar level myelomeningocele is clinically challenging. Muscle transfer procedures, release of contractures, and intertrochanteric varus-rotation osteotomies have been described to restore weak or absent abductor strength as well as relocation of the hip. However, controlled trials evaluating hip instability in lower lumbar myelomeningocele are limited in the current literature., Questions/purposes: The purposes of this study were to compare the (1) radiographic evidence for joint stability; (2) clinical outcomes (including abductor strength, ambulatory ability, and residual use of orthoses); and (3) complications between patients undergoing combined periarticular contracture releases and bony procedures with and without external oblique abdominal muscle transfers., Methods: Between 2004 and 2013, 14 pediatric patients (16 hips) were treated for hip instability secondary to myelomeningocele using releases with or without muscle transfer. From those, 13 patients (15 hips) with a mean age of 6 years who had L3 to L5 level involvement were evaluated retrospectively. The patients were separated into two groups. Nine hips (in eight patients) were treated by performing a combination of external oblique abdominal muscle transfer to the greater trochanter, periarticular release of contractures, and bony procedures. These were compared with six hips (five patients) treated by performing a combination of periarticular release of contractures and bony procedures without external oblique abdominal muscle transfer. This study compared the results between two surgeons, one of whom always performed these muscle transfers in this setting and the other who never performed muscle transfer during the study period. The patients were clinically followed up at a mean of 41 months (range, 14-122 months); none of the patients was lost to followup. Radiographic evaluation criteria included Reimer's migration index, acetabular index, femoral neck-shaft angle, pelvic obliquity, and the presence of scoliosis. Clinical evaluation included muscle strength examination, periarticular contractures, necessity for using orthoses as walking aids, and Hoffer criteria of mobility. All complications were also noted from a chart review., Results: There were no differences between the two groups regarding postoperative femoral head localization, reflecting the presence or absence of residual subluxation, according to Reimer's index (Reimer's index = 32%; range, 10%-40%, in the muscle transfer group compared with 27%; range, 15%-43%, in the no-transfer group at latest followup; p = 0.723). Postoperatively, abductor strength improved in the group treated with external oblique transfer compared with the group treated without muscle transfer (median improvement of 2 versus 0, p = 0.02), but this improvement neither resulted in a clinically important difference in Hoffer criteria of mobility (no change was detected in either group) nor decreased the need for use of an orthosis (no change was detected in either group). With the numbers available, there was no difference with respect to complications between the two groups (two complications versus one)., Conclusions: External oblique abdominal muscle transfer did not provide a clinically important improvement in functional recovery when compared with patients with L3 to L5 myelomeningocele and hip instability who were treated without it. We therefore do not recommend a routine muscle transfer procedure during the operative management of hip instability in patients with lower lumbar level myelomeningocele., Level of Evidence: Level III, therapeutic study.