Hyperphagia in Prader-Willi syndrome: linking hypothalamic dysfunction to clinical assessment and management across the lifespan.

Abstract

Background: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterised by hypothalamic dysfunction and profound dysregulation in hunger and appetite regulation, endocrine function, metabolism and behaviour. Hyperphagia is a defining clinical feature and a major contributor to morbidity, mortality and caregiver burden. Increasing evidence suggests that hyperphagia in PWS represents a multidimensional disorder rather than excessive appetite alone.

Results: In December 2024, an international meeting of clinical and scientific experts was convened in Toulouse, France, to explore current understanding of hyperphagia in PWS, challenges in assessment, and evolving approaches to management across the lifespan. Although not a formal consensus process, several consistent themes emerged. These included limitations of existing assessment tools, the need for multidimensional evaluation (including use of instruments such as the Hyperphagia Questionnaire and Hyperphagia Questionnaire for Clinical Trials (HQ-CT). The central role of structured food environments, and vulnerabilities during transition to adult care were also identified as key themes. Experts emphasised that hyperphagia reflects interactions between impaired satiety signalling, activation in reward neurocircuitry, autonomic dysfunction and environmental factors. Management therefore requires integrated biological, behavioural and environmental approaches. While food security and structured support remain foundational, emerging pharmacological therapies may complement multidisciplinary care and reduce caregiver burden.

Conclusions: Hyperphagia in PWS should be conceptualised as a complex, multidimensional disorder requiring comprehensive assessment and integrated management. Future priorities include development of additional validated outcome measures, identification of biomarkers, and care models that better align mechanistic insights with real-world clinical practice.