Hyperphagia in Prader–Willi syndrome: linking hypothalamic dysfunction to clinical assessment and management across the lifespan
Orphanet Journal of Rare Diseases, vol. 21
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.
Authors 19
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M. Tauber corresponding
Centre National de la Recherche Scientifique · Université Toulouse III - Paul Sabatier · Inserm · Université Fédérale de Toulouse Midi-Pyrénées
Affiliation as printed
Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire) and European Reference Network on Rare Endocrine Conditions (Endo-ERN), Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France. tauber.mt@chu-toulouse.fr
Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), INSERM UMR1291-CNRS UMR5051-Université Toulouse III, Toulouse, 31062, France. tauber.mt@chu-toulouse.fr
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Centre National de la Recherche Scientifique · Université Toulouse III - Paul Sabatier · Inserm · Institut Toulousain des Maladies Infectieuses et Inflammatoires
Affiliation as printed
Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire) and European Reference Network on Rare Endocrine Conditions (Endo-ERN), Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), INSERM UMR1291-CNRS UMR5051-Université Toulouse III, Toulouse, 31062, France
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Sorbonne Université · Pitié-Salpêtrière Hospital
Affiliation as printed
Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Department of Nutrition and European Reference Network on Rare Endocrine Conditions (Endo-ERN), Pitié-Salpêtrière Hospital, Paris, France
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Karolinska University Hospital
Affiliation as printed
Department of Endocrinology and Department of Molecular Medicine and Surgery and European Reference Network on Rare Endocrine Conditions (Endo-ERN), Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
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Queen Mary University of London · Barts Health NHS Trust · Royal London Hospital · Genomics England
Affiliation as printed
Centre for Endocrinology, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK
Department of Paediatric Endocrinology, Royal London Children's Hospital, Barts Health NHS Trust Royal London Children's Hospital, Whitechapel, London, E1 1FH, UK
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Hammersmith Hospital · Imperial College London
Affiliation as printed
PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK
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Affiliation as printed
University of Alberta, Alberta, Canada
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The University of Sydney · Children's Hospital at Westmead
Affiliation as printed
The Children's Hospital at Westmead, Sydney, Australia
University of Sydney, Sydney, Australia
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Vanderbilt University Medical Center
Affiliation as printed
Vanderbilt University Medical Center, Nashville, TN, USA
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Affiliation as printed
Pittsburgh Partnership, Pittsburgh, PA, USA
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Affiliation as printed
Department of Psychiatry, University of Cambridge, Cambridge, UK
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Affiliation as printed
Department of Psychiatry, University of Cambridge, Cambridge, UK
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Laura de Graaff Aachen Dutch Center of Reference for Prader-Willi Syndrome and European Reference Network on Rare Endocrine Conditions (Endo-ERN)
Affiliation as printed
Division of Endocrinology, Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Dutch Center of Reference for Prader-Willi Syndrome and European Reference Network on Rare Endocrine Conditions (Endo-ERN), Rotterdam, The Netherlands
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University of Kansas Medical Center
Affiliation as printed
University of Kansas Medical Center, Kansas City, KS, USA
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Institute of Research and Innovation Parc Tauli
Affiliation as printed
Endocrinology and Nutrition Department, Consorci Corporació Sanitària Parc Taulí. Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Medicine Department Universitat Autònoma de Barcelona, Sabadell, Spain
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Queen Mary University of London · Blizard Institute
Affiliation as printed
Blizard Institute, Queen Mary University, London, UK
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Neurocrine Biosciences (United States)
Affiliation as printed
Soleno Therapeutics Europe, a Neurocrine Biosciences Company, Dublin, Ireland
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Neurocrine Biosciences (United States)
Affiliation as printed
Soleno Therapeutics Europe, a Neurocrine Biosciences Company, Dublin, Ireland
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University of Florida Health · University of Florida
Affiliation as printed
Division of Endocrinology, Department of Pediatrics, University of Florida, Gainesville, FL, USA