What is PWS?
Prevalence of PWS
Clinical features of PWS
Clinical features associated with PWS may vary but often begin with neonatal hypotonia and poor feeding in infancy, followed by hyperphagia (pathological, insatiable hunger and impaired satiety accompanied by abnormal food-seeking behaviors) and early-onset, severe obesity in childhood into adulthood.3-7
- Endocrine abnormalities, including growth hormone deficiency and hypogonadism
- Body composition abnormalities
- Intellectual disability
- Behavioral difficulties
- Dysmorphic features
The relationship between PWS and the melanocortin-4 receptor (MC4R) pathway
An important component of the underlying disease biology is genetic variations within a region on chromosome 15 that may impact signaling within the MC4R pathway, which plays a key role in the regulation of energy balance.6,8-14
A majority of people with PWS lack expression of genes involved in the development and function of the MC4R pathway, including MAGEL2 and SNORD115. The loss of these genes may result in decreased alpha-melanocyte-stimulating hormone (α-MSH) and impaired MC4R pathway signaling, contributing to the hyperphagia and severe obesity observed in people with PWS.6,8-14
There remains a clear and significant need for more treatment options for people with hyperphagia and severe obesity associated with PWS.15,16
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α-MSH, alpha-melanocyte-stimulating hormone; MC4R, melanocortin-4 receptor; PWS, Prader-Willi syndrome
References
1. Daley SF, Fermin Gutierrez MA, Mendez MD. Prader-Willi Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 2, 2025. 2. Butler MG, et al. Curr Pediatr Rev. 2016;12(2):136-166. 3. Huvenne H, et al. Obes Facts. 2016;9:158-173. 4. Cassidy SB, Driscoll DJ. Eur J Hum Genet. 2009;17(1):3-13. 5. Heymsfield SB, et al. Obesity (Silver Spring). 2014;22(suppl 1):S1-S17. 6. Hampl SE, et al. Pediatrics. 2023;151(2):e2022060640. 7. Driscoll DJ, et al. Prader-Willi Syndrome. 1998 Oct 6 [Updated 2024 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. 8. Prader-Willi Syndrome Association. The Genetics of Prader-Willi Syndrome:An Explanation for the Rest of US. Retrieved September 24, 2025, from https://www.pwsausa.org/wp-content/uploads/2022/12/Genetics-of-PWS-%E2%80%93-An-Explanation-for-the-Rest-of-Us.pdf 9. Garfield AS, et al. Mol Brain. 2016;9(1):95. 10. Chen H, et al. JCI Insight. 2020;5(17):e138576. 11. Mercer RE, et al. PLoS Genet. 2013;9(1):e1003207.Endocrinol Metab. 2011;22:286-293. 12. Bochukova EG et al. Cell Rep. 2018;22(13):3401-3408. 13. Turkkahraman D, et al. J Endocrinol Invest. 2022;45(5):1031-1037. 14. Pravdivyi I, et al. Hum Mol Genet. 2015;24(15):4276-4283. 15. Calcaterra V, et al. Children (Basel). 2023;10(3):564. 16. Duis J, et al. Mol Genet Genomic Med. 2019;7(3):e514.
