The role of genetics and molecular mechanisms in early onset scoliosis

Early onset scoliosis (EOS), a spinal deformity that occurs before 10 years of age, imposes significant morbidity due to its rapid Cobb angle progression, three-dimensional spinal curvature, and potential respiratory compromise from thoracic cage distortion. This condition, classified into idiopathic, congenital, neuromuscular, and syndromic subtypes, exhibits high phenotypic heterogeneity and multisystem involvement. Current treatments like bracing and surgery focus on modulating curve progression and preserving growth, but the genetic and molecular overview is not clear. This review delineates both the genetic basis and the pathogenic mechanisms of EOS. We summarize 79 genes implicated in EOS subtypes and discuss the underlying pathogenetic mechanisms, including somitogenesis defects, abnormal vertebral development, and neuromuscular disorders. We also highlight emerging therapeutic strategies and discuss future directions. By integrating genetic discoveries with molecular pathophysiology, this review provides a foundation for advancing precision medicine in EOS and highlights critical future research directions in the field.