Dimeglio Score Predicts Treatment Difficulty During Ponseti Casting for Isolated Clubfoot.

BACKGROUND: The Dimeglio score (DS) is widely used to assess clubfoot severity, but its ability to predict long-term outcomes following Ponseti treated isolated clubfoot (IC) is controversial. This study tested the association between the initial DS and its individual parameters with the number of Ponseti clubfoot casts required to achieve correction and the rate of early recurrence following treatment. METHODS: Data were retrospectively collected from patients who underwent treatment of IC between March 2012 and March 2015 and were followed for ≥2 years. DSs were collected at the initial casting visit. The number of Ponseti casts required to achieve clubfoot correction before tenotomy and recurrence of deformity were collected as the primary outcome variables. Recurrence was defined as any loss of correction leading to repeat casting or tenotomy during the bracing phase. Negative binomial and logistic regression analyses were used to test the association between the 8 Dimeglio parameters and number of casts and incidence of recurrence, respectively. RESULTS: A total of 53 patients (37 male and 16 female) were included in the study. The median number of casts required to achieve an acceptable correction was 5 (range, 2 to 16). The incidence of recurrence was 24.53% (13/53). An increase in derotation, varus, equinus, muscle condition, and total DSs at the initial cast visit were associated with a significant (P<0.05) increase in the number of casts required to achieve an acceptable correction. The derotation parameter [rate ratio: 1.30, 95% confidence interval (CI): 1.13-1.50, P=0.0003] was most strongly associated with number of casts. Total DSs at initial visit was the only variable significantly associated with the incidence of deformity recurrence (odds ratio: 1.36, 95% confidence interval: 1.01-1.84, P=0.0482). CONCLUSION: Initial DS is correlated with the number of casts required for correction in Ponseti treated IC. DS may help physicians establish realistic expectations for families with regard to the length of treatment and the possibility of recurrence following Ponseti treatment. LEVEL OF EVIDENCE: Level II-retrospective prognostic study.

Whole Exome Sequencing of 23 Multigeneration Idiopathic Scoliosis Families Reveals Enrichments in Cytoskeletal Variants, Suggests Highly Polygenic Disease.

Adolescent idiopathic scoliosis (AIS) is a lateral spinal curvature >10° with rotation that affects 2-3% of healthy children across populations. AIS is known to have a significant genetic component, and despite a handful of risk loci identified in unrelated individuals by GWAS and next-generation sequencing methods, the underlying etiology of the condition remains largely unknown. In this study, we performed exome sequencing of affected individuals within 23 multigenerational families, with the hypothesis that the occurrence of rare, low frequency, disease-causing variants will co-occur in distantly related, affected individuals. Bioinformatic filtering of uncommon, potentially damaging variants shared by all sequenced family members revealed 1448 variants in 1160 genes across the 23 families, with 132 genes shared by two or more families. Ten genes were shared by >4 families, and no genes were shared by all. Gene enrichment analysis showed an enrichment of variants in cytoskeletal and extracellular matrix related processes. These data support a model that AIS is a highly polygenic disease, with few variant-containing genes shared between affected individuals across different family lineages. This work presents a novel resource for further exploration in familial AIS genetic research.

Implementation of a Ponseti Clubfoot Program Decreases Major Surgery: A Quality Improvement Initiative.

Clubfoot describes a congenital condition. If untreated, clubfoot can cause long-term functional issues. The Ponseti method is the gold-standard treatment; it emphasizes casting over surgery. We identified a high rate of major recurrence in patients with isolated clubfoot at our institution. We implemented a quality improvement intervention to address the recurrences. METHODS: We established a clubfoot program that aimed to (1) develop a standardized treatment pathway; (2) improve care team education; (3) improve coordination of care with families; and (4) improve documentation. The purpose of this study was to outline our quality improvement intervention and evaluate its success. Data were retrospectively collected from isolated clubfeet before (2003-2007, phase I) and after (2012-2014, phase II) implementation of the clubfoot program. We compared the differences in treatment and major recurrence between the 2 phases using generalized logistic or linear mixed models. Modified Poisson regression models were used to evaluate the association between provider nonadherence and recurrence. RESULTS: The pre- (phase I) and post- (phase II) implementation groups included 91 patients (131 feet) and 68 patients (101 feet), respectively. The incidence of major recurrence (odds ratio: 59.5, 95% confidence interval: 7.8-454.4, P < 0.0001) was lower during phase II compared to phase I. Nonadherence with the care pathway was associated with an increased risk of recurrence (risk ratio: 4.1, 95% confidence interval: 1.2-14.3, P = 0.0274). CONCLUSIONS: The implementation of a clubfoot program was associated with a decrease in major clubfoot surgery and improved adherence to established guidelines for clubfoot management.

A comparison of fixation methods in adolescent patients with diaphyseal forearm fractures.

INTRODUCTION: The purpose of this study was to compare both bone diaphyseal forearm fractures in adolescent patients treated with plate fixation to patients treated with intramedullary fixation to identify differences in complications and outcomes. MATERIALS & METHODS: A retrospective study was performed on all adolescent patients with age between 10 and16 year and treated with intramedullary fixation or plate fixation for a diaphyseal both bone forearm fracture between 2005 and 2014. Demographic information and clinical data was collected. Radiographs were reviewed to evaluate post-operative radial bow magnitude and location, time to union, and residual angulation. Complications were graded using the modified Clavien-Dindo Classification system. RESULTS: A total of 102 patients met the inclusion criteria. Of these, 32 were treated with plate fixation and 70 with intramedullary fixation. The intramedullary nail group had 55% of complications classified as major. There were no major complications in the plate fixation group (P = 0.1). The radial bow was significantly more distal and smaller in magnitude in the intramedullary fixation group (P < 0.01). Of the patients who underwent intramedullary fixation, 76% required an open reduction of at least one forearm bone. There was increased time to radiographic union in patients treated with intramedullary fixation when compared to those treated with plates, 68 days versus 58 days (P = 0.03). A second operation was necessary for 91% of patients treated with intramedullary fixation compared to only 3% of patients treated with a plate (P < 0.01). CONCLUSION: Diaphyseal forearm fractures in adolescent patients remain challenging injuries to treat. Forearm bony anatomy is not completely restored with intramedullary fixation. Results suggested an association towards increased complication rates and complication severity with intramedullary fixation. LEVEL OF EVIDENCE: Level 3 retrospective comparative study.

Idiopathic Scoliosis Families Highlight Actin-Based and Microtubule-Based Cellular Projections and Extracellular Matrix in Disease Etiology.

Idiopathic scoliosis (IS) is a structural lateral spinal curvature of ≥10° that affects up to 3% of otherwise healthy children and can lead to life-long problems in severe cases. It is well-established that IS is a genetic disorder. Previous studies have identified genes that may contribute to the IS phenotype, but the overall genetic etiology of IS is not well understood. We used exome sequencing to study five multigenerational families with IS. Bioinformatic analyses identified unique and low frequency variants (minor allele frequency ≤5%) that were present in all sequenced members of the family. Across the five families, we identified a total of 270 variants with predicted functional consequences in 246 genes, and found that eight genes were shared by two families. We performed GO term enrichment analyses, with the hypothesis that certain functional annotations or pathways would be enriched in the 246 genes identified in our IS families. Using three complementary programs to complete these analyses, we identified enriched categories that include stereocilia and other actin-based cellular projections, cilia and other microtubule-based cellular projections, and the extracellular matrix (ECM). Our results suggest that there are multiple paths to IS and provide a foundation for future studies of IS pathogenesis.

Sequencing of the TBX6 Gene in Families with Familial Idiopathic Scoliosis.

STUDY DESIGN: A hypothesis-driven study was conducted in a familial cohort to determine the potential association between variants within the TBX6 gene and Familial Idiopathic Scoliosis (FIS). OBJECTIVE: To determine if variants within exons of the TBX6 gene segregate with the FIS phenotype within a sample of families with FIS. SUMMARY OF BACKGROUND DATA: Idiopathic Scoliosis (IS) is a structural curvature of the spine whose underlying genetic etiology has not been established. IS has been reported to occur at a higher rate than expected in family members of individuals with congenital scoliosis (CS), suggesting that the two diseases might have a shared etiology. The TBX6 gene on chromosome 16p, essential to somite development, has been associated with CS in a Chinese population. Previous studies have identified linkage to this locus in families with FIS, and specifically with rs8060511, located in an intron of the TBX6 gene. METHODS: Parent-offspring trios from 11 families (13 trios, 42 individuals) with FIS were selected for Sanger sequencing of the TBX6 gene. Trios were selected from a large population of families with FIS in which a genome-wide scan had resulted in linkage to 16p. RESULTS: Sequencing analyses of the subset of families resulted in the identification of five coding variants. Three of the five variants were novel; the remaining two variants were previously characterized and account for 90% of the observed variants in these trios. In all cases, there was no correlation between transmission of the TBX6 variant allele and FIS phenotype. However, an analysis of regulatory markers in osteoblasts showed that rs8060511 is in a putative enhancer element. CONCLUSIONS: Although this study did not identify any TBX6 coding variants that segregate with FIS, we identified a variant that is located in a potential TBX6 enhancer element. Therefore, further investigation of the region is needed.

Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis.

Idiopathic scoliosis occurs in 3% of individuals and has an unknown etiology. The objective of this study was to identify rare variants that contribute to the etiology of idiopathic scoliosis by using exome sequencing in a multigenerational family with idiopathic scoliosis. Exome sequencing was completed for three members of this multigenerational family with idiopathic scoliosis, resulting in the identification of a variant in the HSPG2 gene as a potential contributor to the phenotype. The HSPG2 gene was sequenced in a separate cohort of 100 unrelated individuals affected with idiopathic scoliosis and also was examined in an independent idiopathic scoliosis population. The exome sequencing and subsequent bioinformatics filtering resulted in 16 potentially damaging and rare coding variants. One of these variants, p.Asn786Ser, is located in the HSPG2 gene. The variant p.Asn786Ser also is overrepresented in a larger cohort of idiopathic scoliosis cases compared with a control population (P = 0.024). Furthermore, we identified additional rare HSPG2 variants that are predicted to be damaging in two independent cohorts of individuals with idiopathic scoliosis. The HSPG2 gene encodes for a ubiquitous multifunctional protein within the extracellular matrix in which loss of function mutation are known to result in a musculoskeletal phenotype in both mouse and humans. Based on these results, we conclude that rare variants in the HSPG2 gene potentially contribute to the idiopathic scoliosis phenotype in a subset of patients with idiopathic scoliosis. Further studies must be completed to confirm the effect of the HSPG2 gene on the idiopathic scoliosis phenotype.