Epigenetic and genetic factors related to curve progression in adolescent idiopathic scoliosis: a systematic review of the current literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity, leading in rare cases to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were in-cluded; 15 genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical application. In contrast, 9 studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic test-ing for AIS has the potential to significantly modify disease management. Most recent evidence suggest epigenetics as more promising field for the identification of factors associated to AIS progression, offering a rationale for further investigation in this field.