The burden of illness in Prader-Willi syndrome: a systematic literature review

Abstract Background Prader-Willi syndrome (PWS) is a rare, genetic neurobehavioral and metabolic disorder marked by hyperphagia, behavioral challenges, and significant comorbidities, requiring a multidisciplinary approach for effective management. This systematic review aimed to comprehensively eval...

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Main Authors: Dairine Dempsey, Maria Hall, Ben Lanning, Ben Barron-Millar, Michael Huang, Neil Cowen, Mitch Nagao, Raj Gandhi, Anish Bhatnagar
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Orphanet Journal of Rare Diseases
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Online Access:https://doi.org/10.1186/s13023-025-03787-0
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author Dairine Dempsey
Maria Hall
Ben Lanning
Ben Barron-Millar
Michael Huang
Neil Cowen
Mitch Nagao
Raj Gandhi
Anish Bhatnagar
author_facet Dairine Dempsey
Maria Hall
Ben Lanning
Ben Barron-Millar
Michael Huang
Neil Cowen
Mitch Nagao
Raj Gandhi
Anish Bhatnagar
author_sort Dairine Dempsey
collection DOAJ
description Abstract Background Prader-Willi syndrome (PWS) is a rare, genetic neurobehavioral and metabolic disorder marked by hyperphagia, behavioral challenges, and significant comorbidities, requiring a multidisciplinary approach for effective management. This systematic review aimed to comprehensively evaluate the burden of disease associated with PWS, focusing on mortality, healthcare resource utilization, economic burden, and quality of life. Methods The literature search, conducted on August 13, 2024, included the MEDLINE, Embase, and Cochrane Library databases, as well as conference proceedings. Original studies published since 2014 were selected based on relevance to PWS patient burden, covering mortality, humanistic and economic impacts. Data from the selected studies were extracted, and currency conversions were standardized. Results For the topics of mortality, humanistic burden and economic burden, a total of 11 studies, 95 studies, and 33 studies were included, respectively. Individuals with PWS faced significantly reduced life expectancy compared to the general population, with leading causes of death including respiratory failure, consequences of uncontrolled hyperphagia, and cardiovascular complications. Hyperphagia contributed substantially to the disease burden, necessitating constant food security measures to prevent life-threatening complications. Primary caregivers, predominantly parents of individuals with PWS, experienced significant emotional and psychological strain. The time-intensive responsibilities of implementing food security measures heavily impacted their daily lives, social and family dynamics, as well as their financial health. Quality of life for patients was less frequently reported but markedly impaired, driven by physical health challenges, behavioral issues, and social isolation. Wider family dynamics were also often impacted, with siblings reporting increased psychosocial stress and feelings of neglect. The direct costs of managing PWS, including frequent hospitalizations and specialized care, were consistently reported to exceed those of matched controls without PWS, highlighting the substantial economic burden associated with the condition. Conclusion This systematic literature review highlights the profound burden of PWS on patients, caregivers, payers of care, and healthcare systems. Complications of PWS reduce life expectancy, impair quality of life, and impose considerable financial strain. The findings underscore an urgent need for comprehensive support and innovative treatments that address the complex manifestations and consequences of PWS, particularly hyperphagia, to improve outcomes for patients and their families.
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spelling doaj-art-14fa2c6c3eb74751953c99f069f1824e2025-08-20T03:06:05ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-0120112510.1186/s13023-025-03787-0The burden of illness in Prader-Willi syndrome: a systematic literature reviewDairine Dempsey0Maria Hall1Ben Lanning2Ben Barron-Millar3Michael Huang4Neil Cowen5Mitch Nagao6Raj Gandhi7Anish Bhatnagar8Soleno Therapeutics Europe LtdMaria Hall Consulting LtdKintigaKintigaSoleno Therapeutics, IncSoleno Therapeutics, IncSoleno Therapeutics, IncSoleno Therapeutics, IncSoleno Therapeutics, IncAbstract Background Prader-Willi syndrome (PWS) is a rare, genetic neurobehavioral and metabolic disorder marked by hyperphagia, behavioral challenges, and significant comorbidities, requiring a multidisciplinary approach for effective management. This systematic review aimed to comprehensively evaluate the burden of disease associated with PWS, focusing on mortality, healthcare resource utilization, economic burden, and quality of life. Methods The literature search, conducted on August 13, 2024, included the MEDLINE, Embase, and Cochrane Library databases, as well as conference proceedings. Original studies published since 2014 were selected based on relevance to PWS patient burden, covering mortality, humanistic and economic impacts. Data from the selected studies were extracted, and currency conversions were standardized. Results For the topics of mortality, humanistic burden and economic burden, a total of 11 studies, 95 studies, and 33 studies were included, respectively. Individuals with PWS faced significantly reduced life expectancy compared to the general population, with leading causes of death including respiratory failure, consequences of uncontrolled hyperphagia, and cardiovascular complications. Hyperphagia contributed substantially to the disease burden, necessitating constant food security measures to prevent life-threatening complications. Primary caregivers, predominantly parents of individuals with PWS, experienced significant emotional and psychological strain. The time-intensive responsibilities of implementing food security measures heavily impacted their daily lives, social and family dynamics, as well as their financial health. Quality of life for patients was less frequently reported but markedly impaired, driven by physical health challenges, behavioral issues, and social isolation. Wider family dynamics were also often impacted, with siblings reporting increased psychosocial stress and feelings of neglect. The direct costs of managing PWS, including frequent hospitalizations and specialized care, were consistently reported to exceed those of matched controls without PWS, highlighting the substantial economic burden associated with the condition. Conclusion This systematic literature review highlights the profound burden of PWS on patients, caregivers, payers of care, and healthcare systems. Complications of PWS reduce life expectancy, impair quality of life, and impose considerable financial strain. The findings underscore an urgent need for comprehensive support and innovative treatments that address the complex manifestations and consequences of PWS, particularly hyperphagia, to improve outcomes for patients and their families.https://doi.org/10.1186/s13023-025-03787-0Burden of illnessDirect costsIndirect costsCaregiver burdenHealth-related quality of lifeHumanistic burden
spellingShingle Dairine Dempsey
Maria Hall
Ben Lanning
Ben Barron-Millar
Michael Huang
Neil Cowen
Mitch Nagao
Raj Gandhi
Anish Bhatnagar
The burden of illness in Prader-Willi syndrome: a systematic literature review
Orphanet Journal of Rare Diseases
Burden of illness
Direct costs
Indirect costs
Caregiver burden
Health-related quality of life
Humanistic burden
title The burden of illness in Prader-Willi syndrome: a systematic literature review
title_full The burden of illness in Prader-Willi syndrome: a systematic literature review
title_fullStr The burden of illness in Prader-Willi syndrome: a systematic literature review
title_full_unstemmed The burden of illness in Prader-Willi syndrome: a systematic literature review
title_short The burden of illness in Prader-Willi syndrome: a systematic literature review
title_sort burden of illness in prader willi syndrome a systematic literature review
topic Burden of illness
Direct costs
Indirect costs
Caregiver burden
Health-related quality of life
Humanistic burden
url https://doi.org/10.1186/s13023-025-03787-0
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