Endocrine-informed monitoring of scoliosis in Prader-Willi syndrome: integrating neuroendocrine pathophysiology, growth hormone therapy, and pubertal transition.

Prader-Willi syndrome (PWS) is a neuroendocrine disorder characterized by hypothalamic dysfunction, congenital hypotonia, abnormal growth trajectories, and impaired pubertal development, all of which contribute to a markedly increased risk of scoliosis, with a cumulative prevalence reaching up to 70-80% by skeletal maturity, significantly exceeding that of idiopathic scoliosis. Unlike idiopathic scoliosis, spinal deformity in PWS follows a distinct bimodal pattern, with critical vulnerability during infancy and a second acceleration during pubertal transition. Growth hormone (GH) therapy, a cornerstone of PWS management, substantially improves linear growth, body composition, and muscle strength, yet its relationship with scoliosis onset and progression remains a clinical challenge due to the potential for accelerated growth during critical developmental windows, which may unmask or exacerbate underlying spinal instability. Current scoliosis surveillance strategies in PWS are largely extrapolated from idiopathic scoliosis and fail to account for the unique neuroendocrine and biomechanical context of this syndrome. In particular, endocrine modifiers such as GH treatment status, growth velocity, hypogonadism, pubertal stage, body composition, and genotype-specific phenotypes are rarely integrated into structured monitoring protocols. In this narrative review, we synthesize epidemiological, mechanistic, and clinical evidence to elucidate the neuroendocrine and biomechanical pathways underlying scoliosis development in PWS, including the roles of hypotonia-related instability, altered vertebral growth modulation, and delayed epiphyseal maturation. We critically examine the dualistic effects of GH therapy, the impact of pubertal maturation, and genotype-phenotype associations as key determinants of scoliosis risk and progression. Building on this evidence, we propose an endocrine-informed, risk-stratified scoliosis monitoring framework that integrates growth dynamics, hormonal status, body composition, and spinal parameters to guide surveillance intensity, imaging strategies, and multidisciplinary referral. By shifting the focus from isolated curve detection to longitudinal, endocrine-guided surveillance, this review provides a clinically actionable model to optimize early identification and management of scoliosis in children and adolescents with PWS. This framework aims to support coordinated endocrine-orthopedic care and inform future prospective studies designed to refine outcome measures and ultimately improve long-term musculoskeletal and quality-of-life outcomes in this vulnerable population.