Molecular diagnosis and novel genes and phenotypes in a pediatric thoracic insufficiency cohort.

Thoracic insufficiency syndromes are a genetically and phenotypically heterogeneous group of disorders characterized by congenital abnormalities or progressive deformation of the chest wall and/or vertebrae that result in restrictive lung disease and compromised respiratory capacity. We performed whole exome sequencing on a cohort of 42 children with thoracic insufficiency to elucidate the underlying molecular etiologies of syndromic and non-syndromic thoracic insufficiency and predict extra-skeletal manifestations and disease progression. Molecular diagnosis was established in 24/42 probands (57%), with 18/24 (75%) probands having definitive diagnoses as defined by laboratory and clinical criteria and 6/24 (25%) probands having strong candidate genes. Gene identified in cohort patients most commonly encoded components of the primary cilium, connective tissue, and extracellular matrix. A novel association between KIF7 and USP9X variants and thoracic insufficiency was identified. We report and expand the genetic and phenotypic spectrum of a cohort of children with thoracic insufficiency, reinforce the prevalence of extra-skeletal manifestations in thoracic insufficiency syndromes, and expand the phenotype of KIF7 and USP9X-related disease to include thoracic insufficiency.

Changes in research quality and surgical trends at the international congress on early-onset scoliosis.

PURPOSE: The founding of the International Congress for Early Onset Scoliosis (ICEOS) and first annual meeting in 2007 represented a significant milestone in advancing the care of patients with EOS. Due to the complexity and rarity of EOS, this annual conference is the premiere venue for physicians, researchers, and advanced practice providers to identify and understand the best treatments for children with EOS. This study examines the trend of various treatment modalities presented at ICEOS and the changes in research quality since its inception. METHODS: Podium presentations from the 2007 through 2021 ICEOS annual meetings were reviewed to determine the number of study patients, use of a study group, and key features of study design. Treatment strategies being evaluated were recorded and included non-operative treatments (casting/bracing), traditional growing rods (TGR), vertical expandable prosthetic titanium rib (VEPTR), Shilla growth guidance, magnetically controlled growing rods (MCGR), and vertebral body tethering (VBT). Linear regressions were performed to analyze changes in research topic and study group utilization. RESULTS: A total of 532 abstracts were reviewed. An average of 97.5 ± 81.3 patients were included per study with a significant increase from 42.3 ± 89.7 in 2007 to 337.6 ± 587.4 in 2021 (r2 = 0.632, p < 0.001). A total of 130 (24.4%) abstracts resulted from multicenter study groups with the proportion increasing significantly from 13.0% in 2007 to 36.4% in 2021 (p = 0.039, r2 = 0.289). The majority (96.2%) of study group-based projects were from either the Growing Spine Study Group (GSSG), Chest Wall and Spine Deformity Study Group (CWSDG), Children's Spine Study Group (CSSG), or the Pediatric Spine Study Group (PSSG). Additionally, a significant increase in studies utilizing patient-reported outcome measures (PROMs) was observed (r2 = 0.336, p = 0.023). Significant increases in the proportion of presentations discussing MCGR (r2 = 0.738, p < 0.001) and VBT (r2 = 0.294, p = 0.037) as surgical treatments were observed. CONCLUSION: The trends in EOS device implantation observed in registry studies align with the trends in research presented at ICEOS including the increased proportion of studies focusing on MCGR and VBT over the past decade. An attempt to increase the quality of research presented at ICEOS through multicenter study groups, increased patient recruitment, and utilization of PROMs has been seen since its inception. LEVEL OF EVIDENCE: V.

Weight gain and gastrostomy tube safety during serial body casting for early onset scoliosis.

PURPOSE: Serial casting has been shown to improve curve deformity for patients with early-onset scoliosis (EOS). However, despite prior literature demonstrating the importance of weight and nutrition in EOS patients, there is limited information regarding complications and weight gain ability for children undergoing serial casting. Additionally, parents of patients undergoing serial casting often have concerns regarding weight gain and patient comfort, which tend to be amplified in patients with gastrostomy tubes (g-tubes). We aim to understand changes in weight, g-tube complications, and cast-related complications in patients being treated with serial casting. METHODS: A single center retrospective review of all EOS patients less than 6 years old treated with serial casting was performed. Patient weight out of cast throughout their treatment was converted to a percentile based on CDC growth charts. Patients with documented calls regarding cast concerns, complications requiring cast removal, or g-tube procedures were recorded. RESULTS: A total of 32 patients treated with serial casting were included with four having g tubes. Overall, the average weight percentile increased from pre-casting to post-casting (27-38%, p < 0.001) with 21 patients showing an increase. Of the 22 patients with a starting weight below the 25th percentile, 14 (64%) demonstrated an increase. Patients with g tubes increased an average of 4.2 kg during casting compared to 3.0 kg in patients without g tubes (p = 0.588). 18 parents registered a cast concern during the treatment and 5 patients required at least one early cast removal. No difference in cast concerns (p = 0.597) or cast removals (p = 0.488) was observed when comparing patients with g tubes to those without. There were no instances of g-tube dysfunction during casting. CONCLUSION: While the average weight percentile for patients initiating serial casting is below average, the majority increased their weight percentile during treatment. Patients with and patients without g tubes were able to maintain or gain weight during casting treatment. While it was common for parents to contact providers with cast concerns, patients with g tubes did not appear to have a greater risk of cast or g tube-related complications. LEVEL OF EVIDENCE: Level IV.