肋骨異常を伴う先天性側弯症

Background: Lower-limb deformities in Jarcho-Levin syndrome (JLS) have not been systematically characterized. This study aimed to determine the prevalence and recurrence of lower-limb deformities in patients with JLS and to evaluate factors associated with recurrence and functional outcomes. Methods: A retrospective cohort study was performed at a single center between 2013 and 2024. Patients with a clinical and radiographic diagnosis of JLS and a minimum 2-year follow-up were included. Demographic, neurologic, radiographic, treatment, recurrence, and functional outcome data were reviewed. Recurrence was defined as return of a treated deformity requiring repeat casting, bracing modification, additional surgery, or other intervention. Results: A total of 114 patients were included. Mean follow-up was 6.2 ± 4.3 years. Lower-limb deformity was identified in 94 patients (82.5%); 73 had bilateral involvement. Foot deformity occurred in 76 patients, most commonly pes equinovarus (64 patients), hip dislocation was identified in 79 patients, and hip flexion contracture was identified in 75 patients. Among treated deformities, recurrence was most common after treatment of pes equinovarus, occurring in 29 of 61 patients. Recurrence occurred in 12 of 35 treated hip dislocations, 17 of 49 hip flexion contractures, 9 of 28 knee flexion contractures, and 3 of 8 congenital patellar dislocations. Patients with more frequent recurrence had bilateral involvement, neural tube defects, and multiple deformities, and lower PODCI mobility and global functioning scores. Conclusions: Lower-limb deformities are common, frequently bilateral, and often recurrent in patients with JLS. These findings suggest that careful lower-limb evaluation and long-term follow-up after treatment are important in this population.

Jarcho-Levin syndrome (JLS) is a rare genetic disorder characterized by vertebral and rib malformations, with respiratory complications being a leading cause of morbidity and mortality. Tracheostomy in patients with JLS can be technically challenging due to underlying anatomical abnormalities. We report two cases of JLS in which tracheostomy tube placement was required. In both cases, anatomical deformities presented significant technical challenges during the procedure. Based on our limited experience, we recommend specific surgical considerations for performing tracheostomy in patients with JLS. Furthermore, early tracheostomy should be considered in patients with JLS prior to the development of recurrent pneumonia and pulmonary hypertension. Currently, no standardized guidelines exist regarding the optimal timing of tracheostomy in JLS.

INTRODUCTION: Sprengel deformity is a rare congenital anomaly caused by failure of normal scapular descent during embryogenesis. Spondylocostal dysostosis (SCDO) is a genetically heterogeneous disorder characterized by vertebral segmentation defects and rib malformations. Reports describing the coexistence of these two conditions are scarce, and optimal surgical management remains unclear. CASE REPORT: A 6-year-old girl presented with limited elevation of the left shoulder and visible scapular asymmetry. Imaging demonstrated elevation, medial displacement, and severe downward rotation of the scapula, associated with rib malalignment and cervicothoracic segmentation anomalies consistent with SCDO. We performed a modified Wilkinson procedure incorporating a Y-shaped scapular osteotomy to achieve both caudal repositioning and rotational correction. CONCLUSION: At 1 year postoperatively, shoulder elevation was nearly symmetric, and at 18 months, the patient had no functional limitations. In cases of Sprengel deformity associated with SCDO, severe downward rotation may necessitate a rotationally corrective osteotomy rather than descent alone.

BACKGROUND/OBJECTIVES: Spondylocostal dysostosis (SCDO) is a rare disorder characterized by congenital malformations of the spine and ribs. SCDO affects 1 in 40,000 human births, with rare cases also reported in dogs. Mutations in DLL3, encoding a critical Notch signaling pathway ligand, account for a majority of human SCDO cases. The remaining cases have variants in HES7, LFNG, MESP2, RIPPLY2, TBX6, and DLL1, which code for proteins in the Notch pathway. A mixed-breed litter of three dogs presented with varying degrees of spinal malformations and underwent comprehensive phenotyping including radiographic and neurologic examination. Two littermates demonstrated classic SCDO features including shortened torsos, vertebral malformations, and rib abnormalities, while a third showed only caudal vertebral truncation. METHODS: Short-read whole-genome sequencing was performed on all three animals, followed by variant filtering and analysis using the two severely affected dogs as cases and 173 control dogs of various breeds. Variants were prioritized based on segregation patterns, population frequency, and predicted functional impact using established bioinformatics tools. RESULTS: Variant analysis identified a novel splice acceptor variant in DLL3 (c.650-2A>C). This mutation, located at the splice acceptor site preceding exon 5, is predicted to disrupt critical EGF-like domains and O-fucosylation sites essential for DLL3 protein function. CONCLUSIONS: This study identifies a DLL3 splice variant causing SCDO in dogs, demonstrating phenotypic conservation with humans. These findings refine our understanding of genotype-phenotype correlations and demonstrate the value of comparative genomics for rare developmental disorders.

Spondylocostal dysostosis type 1 is caused by mutations in the DLL3 gene, which encodes a Notch1 ligand. These mutations lead to defective somitogenesis, resulting in a consistent pattern of abnormal vertebral segmentation. Disruptions in the Notch1 signaling pathways can potentially lead to extraskeletal anomalies, although specific associations with DLL3 mutations are less well-documented. We report a 23-week female fetus presenting with characteristic "pebble beach" sign and rib anomalies. Autopsy revealed pulmonary hypoplasia and a 4 mm fundic nodule bulging on both inner and outer gastric surfaces. Histological examination of the stomach walls revealed multifocal pancreatic heterotopia in the fundus and pylorus, invading the submucosa and/or the muscularis propria. Genetic analysis confirmed a novel homozygous likely pathogenic frameshift variant in DLL3 (NM_000435.3:c.183_184del, p.Arg61Serfs*39). This case report expands the DLL3 mutational spectrum in spondylocostal dysostosis type 1 and highlights associated pancreatic heterotopia.