What is Prader-Willi syndrome?
Prader-Willi syndrome (PRAH-der WILL-ee) is a rare medical disorder caused, in most cases, by a random genetic event. Parents did nothing to cause PWS, and it rarely runs in families, but genetic testing is available to give peace of mind to parents who plan to have more children.
PWS is complex. It has two distinct “stages”, each with its own nutritional phases. Symptoms in infancy through about age 2 years are characterized as Failure to Thrive: low muscle tone (hypotonia), poor feeding, and developmental delays. Hyperphagia defines the second stage, beginning with a heightened interest in food that progresses into a constant, intense drive to eat. As hyperphagia develops, behavioral challenges often begin to surface.
Today more than ever before there are advanced treatment and management strategies that improve many PWS symptoms, including muscle tone, growth, cognition, learning, appetite regulation, and emotional regulation.
Symptoms of Prader-Willi syndrome
PWS is a spectrum disorder; not everyone has all symptoms, and each symptom will vary in degree and severity from person to person. If you suspect a PWS diagnosis, review the clinical criteria below and pursue genetic testing as appropriate.
Some families find it empowering to look ahead at future age-specific symptoms, allowing them to proactively plan and manage what may lie ahead. The clinical criteria below represent untreated and unmanaged symptoms.
Clinical Symptoms in Infants
- Perinatal symptoms include decreased fetal movements, polyhydramnios, and growth restriction.
- Significant global hypotonia, poor Moro reflex, poor suck reflex, weak cry
- Feeding difficulties that often require special feeding techniques
- Breathing difficulties including obstructive sleep apnea, central sleep apnea, and hypoventilation
- Characteristic facial features: almond-shaped eyes, narrow forehead, small down-turned mouth with thin upper lip
- Hypogonadism: small genitalia in males and females, undescended testes in males
- Hypopigmentation: fair coloring compared to family members
- Hip dysplasia, scoliosis
- Excessive daytime sleepiness
- Eye abnormalities including strabismus (usually estropia)
Clinical Symptoms in Young Children without intervention:
- Global developmental delays
- Cognitive impairment, learning disorders
- Eye abnormalities including strabismus (estropia), amblyopia, myopia
- Excessive daytime sleepiness, narcolepsy, cataplexy
- Weight gain without an increase in calories (2 - 4.5 years)
- Hyperphagia: insatiable drive to eat, lack of normal satiety. Excessive weight gain and central obesity (usually begins after age 2 years)
- Higher pain threshold
- Substantially slow metabolic rate
- Hypothalamic hypogonadism
- Scoliosis and/or kyphosis
- Sleep-disordered breathing, central sleep apnea (under age 2 years), obstructive sleep apnea, hypoventilation, excessive daytime sleepiness, narcolepsy, cataplexy
- Small hands and feet
- Articulation challenges, Apraxia of Speech, hypernasal speech, language processing challenges
- Thick viscous saliva
- Absent vomit reflex or elevated vomiting threshold
- Temperature regulation irregularities
- Temperament, emotional regulation, and behavioral challenges beginning after age 2 years
Clinical Symptoms in Older Children and Adults without intervention:
Symptoms in the young children and:
- Hyperphagia: insatiable drive to eat or find food to eat later, lack of normal satiety. Excessive weight gain and central obesity if diet and access to food are not strictly controlled.
- Elevated state of anxiousness
- Behavior problems such as resistance to change, repetitive behaviors, obsessive-compulsive tendencies, restricted thoughts and behaviors, oppositionalism, excessive temper tantrums
- Short stature as compared with the family
- Osteoporosis
- Gastroparesis: slower emptying stomach
- Slow emptying bowel
- Premature adrenarche (pubic hair, underarm hair before age 8)
- Incomplete sexual development
- Skin picking
FAQs
PWS affects both sexes and all races and ethnicities equally, occurring in approximately one in 15,000-20,000 live births. Early diagnosis is critical. Genetic testing can confirm the diagnosis with a sample of blood, analyzed in a specialized laboratory and interpreted by a geneticist.
The “Prader-Willi/Angelman DNA methylation Panel” is the gold-standard diagnostic blood test to confirm or rule out PWS, and is used to diagnose all three subtypes: paternal deletion, maternal uniparental disomy (UPD), and imprinting center deletion. See GeneReviews for details of the PWS testing algorithm.
