肋骨異常を伴う先天性側弯症

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.

Spondylocostal dysostosis (SCDO) is a rare genetic disorder characterized by abnormal development of the axial skeleton, resulting in malformations of the vertebrae and ribs that often impair lung development and lead to significant respiratory morbidity. SCDO is thought to arise from defects in the paraxial presomitic mesoderm, an embryonic tissue that forms the vertebral column and ribs. Pathogenic variants in DLL3, MESP2, LFNG, HES7, TBX6, and RIPPLY2 have been identified in various SCDO subtypes. In addition, a single case of a lethal SCDO-like phenotype caused by a homozygous start-loss variant in DMRT2 has been reported. DMRT2 encodes a transcription factor expressed in the dermomyotome during early somite formation in mice. Here, we describe a newborn with severe costovertebral malformations and dysmorphic features, in whom exome sequencing identified a homozygous loss-of-function variant in DMRT2. The phenotype strikingly overlaps the previous report, further supporting the role of biallelic pathogenic DMRT2 variants in a severe SCDO-like disorder. Notably, our patient also exhibited thymic aplasia and immunodeficiency. A review of the exome sequencing data did not reveal any variant that could account for the immunodeficiency. These features have not been previously associated with SCDO, suggesting a potential phenotypic expansion.