Growth, Puberty, and Metabolic Regulation in Prader-Willi Syndrome: From Pathophysiology to Therapeutic Advances

Prader-Willi syndrome (PWS) is a complex neuroendocrine disorder caused by disruption of paternal genes on 15q11-q13, with hallmark hypothalamic dysfunction spanning growth, pubertal maturation, appetite regulation, sleep, and energy balance. From neonatal hypotonia and early feeding difficulty to later hyperphagia and severe obesity, children and adolescents with PWS follow endocrine trajectories distinct from common pediatric obesity or isolated hypogonadism. Growth hormone therapy has improved linear growth and body composition, yet uncertainties persist around optimal timing and dosing, long-term skeletal outcomes, cardiometabolic effects, and interactions with sleep-disordered breathing. Pubertal development is heterogeneous and often incomplete, and evidence-based protocols for induction, maintenance, and fertility counselling require refinement.

This Research Topic invites mechanistic, clinical, and translational work that links pathophysiology to measurable outcomes - including growth velocity, body composition, bone health, pubertal progression, metabolic risk, sleep quality, and quality of life - and evaluates multidisciplinary models spanning nutrition, endocrinology, sleep medicine, psychology/behavior, and transition to adult services. Studies addressing genotype-phenotype differences (e.g., deletion subtypes, maternal uniparental disomy, imprinting defects) and developmental windows for intervention are especially encouraged.

We welcome papers focusing on, but not limited to:

• Neurobiology and genetics of PWS: hypothalamic circuits, neuropeptides, and genotype-phenotype correlations across deletions, mUPD, and imprinting defects.

• Growth, skeletal health, and GH therapy: initiation/dosing strategies, IGF-1 targets, effects on body composition and bone density, scoliosis monitoring, and cardiometabolic markers.

• Puberty and reproductive endocrinology: diagnostic work-ups for hypogonadism, puberty induction and maintenance regimens, monitoring strategies, and fertility/sexual health counseling.

• Metabolic regulation and sleep-endocrine interactions: hyperphagia mechanisms, energy expenditure, insulin sensitivity/β-cell function, dyslipidemia and NAFLD/MASLD, and the bidirectional effects of OSA/hypoventilation with endocrine therapies.

• Integrated care pathways and equity: multidisciplinary clinic models, transition to adult services, psychosocial and caregiver outcomes, and access considerations across settings.

• Therapeutic innovation, measurement, and trials: structured nutrition and behavioral programs; emerging or adjunctive pharmacotherapies for appetite/weight; safety monitoring; and robust endpoints (densitometry/body-composition approaches, digital/wearable monitoring, biomarkers, patient-reported outcomes) with harmonized data standards.

This Topic focuses on pediatric endocrine mechanisms, evaluation, and hormone-informed management in PWS; adult-only cohorts or studies without endocrine/metabolic outcomes are outside scope.