Prader-Willi syndrome
A complex genomic-imprinting disorder of chromosome 15q11-q13 — neonatal hypotonia and feeding difficulty, then hyperphagia, obesity risk, intellectual disability and behavioural and endocrine features.
Prader-Willi syndrome (PWS) results from loss of paternally expressed genes on chromosome 15q11-q13 — most often a paternal deletion, sometimes maternal uniparental disomy, rarely an imprinting defect. The clinical picture changes with age: profound neonatal hypotonia and feeding difficulty in the first months, then a switch in early childhood to hyperphagia and obesity risk, mild-to-moderate intellectual disability, characteristic behavioural and emotional features, short stature with growth-hormone deficiency, and hypogonadism. Modern multidisciplinary care — including growth hormone — has changed long-term outcomes substantially.
At a glance
- Mechanism
- Loss of paternal 15q11-q13 — deletion (~65%), maternal UPD (~30%), imprinting defect (~5%)
- Neonatal phase
- Severe hypotonia, weak suck, feeding difficulty, failure to thrive
- Childhood phase
- Hyperphagia and obesity risk from around 2–4 years
- Cognition
- Mild-to-moderate intellectual disability; ADHD, anxiety, OCD-like behaviours
- Endocrine
- Growth-hormone deficiency, hypogonadism, central adrenal insufficiency in some
What Prader-Willi syndrome is
Prader-Willi syndrome is the prototype genomic-imprinting disorder. The 15q11-q13 region carries genes that are expressed only from the paternally inherited chromosome. When the paternal copy is lost — by deletion, by maternal uniparental disomy (both 15s come from the mother), or by an imprinting defect — those genes are silent, and the syndrome results.
The clinical course is biphasic. In the neonatal period and first months, infants present with profound hypotonia, weak cry, weak suck, feeding difficulty often requiring gavage feeding, and failure to thrive. Between two and four years of age the picture changes: appetite increases dramatically, weight gain becomes the central problem, and a lifelong risk of hyperphagia-driven obesity begins.
Other features include mild-to-moderate intellectual disability, characteristic facial features, short stature, small hands and feet, hypogonadism, sleep disturbance (including hypersomnia and central sleep apnoea risk), thick saliva, high pain threshold, and behavioural features including skin-picking, anxiety, rigidity and OCD-like patterns.
How the diagnosis is made
Diagnosis is genetic. DNA methylation analysis of the 15q11-q13 imprinting centre identifies more than 99% of cases, regardless of mechanism, and is the first-line test. Once methylation confirms PWS, follow-up testing (chromosomal microarray, UPD studies, sometimes targeted sequencing) defines the underlying mechanism, because this affects recurrence-risk counselling.
The neonatal hypotonia phase is the diagnostic window where early recognition matters most: prompt diagnosis allows early growth-hormone planning, structured feeding and developmental support, and crucially, early family preparation for the hyperphagia phase ahead.
Treatment today
Multidisciplinary care across paediatric endocrinology, neurology, nutrition, physiotherapy, speech and language therapy, psychology and special education is the standard. Growth-hormone therapy, started in infancy or early childhood, improves body composition, strength, growth, and a range of long-term outcomes; current guidelines support starting before two years of age in most children. Sleep-disordered breathing should be screened for and managed before and during growth-hormone therapy.
Hyperphagia management is the long-term core challenge. It rests on a structured food environment (locked food, supervised access), consistent routine, behavioural strategies, school and community education, and ongoing family support. The aim is not weight as an end in itself, but preventing the obesity-related complications that historically defined the syndrome's long-term morbidity.
Behavioural and mental-health support — anxiety, rigidity, mood regulation, occasional psychosis risk in adolescence and adulthood — is part of long-term care.
Pipeline — current and emerging treatments for hyperphagia
The pharmacological frontier in PWS is hyperphagia. Multiple drug classes are in active clinical development: oxytocin and oxytocin analogues, the MC4R agonist setmelanotide (approved for several genetic obesity disorders, under evaluation for PWS), GLP-1 receptor agonists, and others. Diazoxide choline (Vykat XR) was approved by the US FDA in 2025 for hyperphagia in PWS, representing the first specific PWS hyperphagia treatment. Programmes targeting the underlying imprinting biology — including approaches to reactivate the maternal allele of imprinted genes — are at earlier preclinical stages.
How an educational review can help
PWS families navigate a complex multidisciplinary plan from the neonatal period onwards, with new pharmacological options arriving fast. An educational review can pull together the current literature on growth-hormone therapy, hyperphagia management, the new and emerging drug landscape, and the behavioural and mental-health considerations, and prepare focused questions for your treating endocrinology and neurology teams.
It is educational — not a diagnosis, treatment or prescription — and does not replace the care of your child's own clinicians.
Selected sources
- Cassidy SB, Driscoll DJ. Prader-Willi syndrome. GeneReviews. Updated 2023.
- Deal CL et al. Growth hormone research society workshop summary: consensus on Prader-Willi syndrome and use of growth hormone. J Clin Endocrinol Metab. 2013 + updates.
- Miller JL et al. Approach to the hyperphagia of Prader-Willi syndrome. Curr Opin Endocrinol Diabetes Obes. 2020.
- FDA approval of diazoxide choline (Vykat XR) for hyperphagia in PWS, March 2025.
- International Prader-Willi Syndrome Organisation (IPWSO) consensus updates.
Last reviewed: 2026-05-28
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