Erum Naqvi obtained her Ph.D. in Molecular Medicine from Hannover Medical School (Germany) after completing her Masters in Biomedical Science and Bachelors in Microbiology from University of Delhi (India). She has several years of experience as a science writer.
Prader-Willi syndrome (PWS) is a rare genetic condition that affects multiple organ systems, causing both physical and mental symptoms and impairing normal growth and development. Currently, no cure is available, but professional care can improve patients’ quality of life.1,2
The clinical signs and symptoms of PWS and how severe they are depend on the age of the patient. Some features are nonspecific, some are subtle, and others develop gradually over time.1,2
A major universal sign of PWS is severely diminished muscle tone (hypotonia), which causes an infant to look like a “floppy” rag doll with joints (knees and elbows) that are loosely extended instead of fixed.2-4 In some cases, hypotonia is present before birth (prenatal hypotonia), evidenced by decreased fetal movements and an abnormal fetal position. These infants often require special assistance for delivery.2
After birth, infantile hypotonia is associated with lethargy, weak cries, poor responsiveness to stimuli, poor sucking reflex, significantly reduced feeding ability, and poor growth and development. PWS infants with hypotonia may also suffer from cognitive impairment with mild intellectual disability, excessive eating, hyperphagia with central obesity, and hypothalamic hypogonadism leading to genital hypoplasia and pubertal insufficiency.2-4
Although hypotonia regresses over time, it sometimes persists to some extent into adulthood.2
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Feeding and Metabolism Dysfunction
Poor sucking reflex due to hypotonia makes it difficult for an infant to breastfeed. Feeding assistance may be necessary in the first 6 months: a feeding tube,2,5 a manual sucking-assistive device, or a feeding system with one-way flow valves (eg, a feeder bottle with special nipples) that allow milk to flow into the baby’s mouth.4
Babies with PWS have a low metabolic rate and thus a low caloric requirement. Because of this, they may not demand feeding on their own. It is important that special steps be taken to maintain the infant’s weight at an appropriate level, such as checking the weight frequently and adjusting the diet accordingly.2,3
As infants grow into children, usually between 4.5 and 8 years of age, their feeding, appetite, and growth increase. An excessive appetite and a lack of satiety after food consumption develop, leading to an abnormally large consumption of food (hyperphagia). Without intervention, the compulsion to eat may result in destructive behaviors, such as consuming spoiled food or garbage, hoarding food, and stealing food or money (to buy food).2
Because these children have a low metabolic rate, it is important that their caloric intake be restricted so that a healthy weight can be maintained.2
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Overeating, if uncontrolled, may lead to choking, esophageal rupture, intestinal wall perforation, gastrointestinal blockage, rapid weight gain, or morbid obesity. Overeating may further increase the risk for diabetes (usually type 2),1 hypertension, sleep apnea, cardiac insufficiency, respiratory problems, and other complications. Thus, a lifetime of professional care is required.2,3
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Physical Signs of PWS
Signs of Hormone Deficiency
Various physical signs of PWS are attributed to poor regulation of hormones such as growth hormone, thyroid hormone, and adrenalin.2
Children with PWS, in comparison with children of a similar age who do not have PWS, are usually short with reduced muscle mass and increased body fat, which can be attributed to growth hormone deficiency. They may also have very small hands and feet, scoliosis (curved spine), strabismus (misaligned eyes that make it difficult to focus), or hip dysplasia (malformed hip joints).2,4
Hypothyroidism and/or central adrenal insufficiency, which are frequently present in people with PWS, cause the patient’s body to be more at risk for infection and less capable of responding to stress, such as illness or injury.2
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The sex organs of individuals with PWS are usually underdeveloped and function inadequately. The onset of puberty is delayed, with incomplete development at puberty, and most individuals with PWS are infertile.2,3
The male sex organs, including the penis, testicles, and scrotum, may be abnormally small. Cryptorchidism, in which the testicles have not descended from the abdomen into the scrotum, may also be present. The voice of a man with PWS may not deepen completely, and facial hair may be absent.2
In females, the clitoris and vaginal lips may be unusually small. Menstruation is either absent or does not begin until the age of 30 years or later.2
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Distinct Facial Features
Patients with PWS have distinct facial features: narrow nasal bridge, almond-shaped eyes, thin upper lip, triangular mouth, narrow forehead, and long, narrow head (dolichocephaly). These facial features may be noticeable shortly after birth or develop slowly over time.2
Some patients may lack color pigmentation and have unusually fair skin, blonde or light-colored hair, and blue eyes.2
Individuals with PWS, usually adolescents and adults (13 years and older), exhibit intellectual disability ranging from borderline or low- intelligence (learning disabilities) to mild or moderate intellectual impairment (issues with thinking, reasoning, and problem-solving). Language development, speech articulation, and motor milestones, such as sitting up, crawling, standing, and walking, are often delayed.2
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Behavioral and Psychiatric Symptoms
The behavioral and psychiatric problems observed in individuals with PWS may be caused by hormonal imbalances. These include temper tantrums or emotional outbursts, extreme stubbornness, obsessive-compulsive symptoms, manipulative behavior, repetition of questions or statements, skin picking (causing open wounds, scarring, and infection), and difficulty controlling emotions. Psychosis develops in up to approximately 20% of patients in late adolescence or young adulthood.2
Sleep issues are common, including excessive daytime sleepiness, reduced rapid eye movement (REM) latency, disruption of the normal sleep cycle, and obstructive sleep apnea. Many individuals with PWS also have a high pain threshold, a tendency to bruise easily without known cause, and seizures.2
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- Prader-Willi syndrome. MedlinePlus. Accessed July 24, 2023.
- Prader-Willi syndrome. NORD. Accessed July 24, 2023.
- Driscoll DJ, Miller JL, Cassidy SB. Prader-Willi syndrome. GeneReviews® [Internet]. Updated March 9, 2023. Accessed July 24, 2023.
- What are the symptoms of Prader-Willi syndrome (PWS)? NIH – Eunice Kennedy Shriver National Institute of Child Health and Human Development. Accessed July 24, 2023.
- PWS Registry data: tube feeding. Foundation for Prader-Willi Research. Accessed July 24, 2023.
Reviewed by Debjyoti Talukdar, MD, on 7/27/2023.