About Prader-Willi Syndrome

About
Prader-Willi
Syndrome

What is Prader-Willi Syndrome?

Prader-Willi syndrome (pronounced PRAH-der WILL-ee) is a complex, rare genetic disorder that results from an abnormality on the 15th chromosome. Identified in 1956, it occurs in about one in 15,000 live births, in both males and females equally, and in all races.

Though Prader-Willi syndrome is a rare disease, it is one of the ten most common conditions seen in genetics clinics and is the most common genetic cause of obesity that has been identified.

PWS affects growth, metabolism, appetite, behavior, and overall development. Persons with PWS typically have weaker muscles, short stature if not treated with growth hormone, incomplete sexual development, and a chronic feeling of hunger that, coupled with a metabolism that utilizes drastically fewer calories than normal, can lead to excessive eating and life-threatening obesity. The drive to eat is never satisfied no matter how much food is consumed, necessitating constant and continuous supervision.

PWS is a lifelong, life-threatening condition. There is no known cause of PWS, nor is there a cure — yet.

Symptoms of Prader-Willi Syndrome

PWS is a spectrum disorder which means that the degree and severity of symptoms amongst persons diagnosed even with the same subtype of PWS will vary from person to person. If the clinical diagnostic criteria below raise suspicion of PWS, genetic testing using DNA methylation analysis is recommended.

Clinical Symptoms in Infants

• Reduced fetal movement. Other obstetric symptoms may include polyhydramnios, malpresentation, and/or growth restriction
• Significant global hypotonia, poor suck reflex, weak cry
• Failure to thrive: feeding difficulties that often require special feeding techniques
• Characteristic facial features: almond shape eyes, long and narrow head shape, narrowing at the
temples, small down turned mouth with thin upper lip (more likely in those with a deletion)
• Hypogonadism; small genitalia in males and females, male cryptorchidism
• Hypopigmentation. Fair coloring compared to family members (more likely in those with a
deletion)
• Excessive daytime sleepiness, narcolepsy, cataplexy
• Eye abnormalities including strabismus (esotropia more common than exotropia)

Clinical Symptoms in Children and Adults

Young Children:

• Global developmental delays
• Cognitive impairment, learning disorders, impaired judgment
• Eye abnormalities including myopia, amblyopia, strabismus
• Weight gain without increase in calories (20–31 months)
• Hyperphagia: insatiable drive to eat or find food without normal satiety. Excessive weight gain and
central obesity if diet and access to food are not strictly controlled (3+ years)
• High pain threshold
• Hypothalamic hypogonadism
• Scoliosis, kyphosis, kyphoscoliosis
• Sleep disturbance and apneas, narcolepsy, cataplexy
• Small hands and/or feet, narrow hands, straight ulnar borders
• Speech and articulation problems
• Temperature regulation irregularities
• Temperament and behavioral issues
• Thick viscous saliva with crusting at mouth corners

Older Children and Adults:

All of the above symptoms in young children and:
• Hyperphagia. Physiological drive to eat or obtain food without normal satiety. Excessive weight gain and central obesity if diet and access to food are not strictly controlled.
• High pain threshold
• Obsessive and compulsive tendencies
• Incomplete sexual development
• Behavior problems such as excessive temper tantrums, oppositionalism, obsessive-compulsive
tendencies
• Short stature as compared with the family
• Skin picking

How is Prader-Willi Syndrome diagnosed?

Prader-Willi syndrome affects both sexes and all races and ethnicities equally, with the incidence of PWS occurring in approximately one in every 15,000-20,000 births. If Prader-Willi syndrome is suspected, genetic testing can confirm the diagnosis. A sample of blood will be drawn and sent to a specialized laboratory, and interpreted by a specialized physician called a geneticist.

Early diagnosis is critical for improving the prognosis. As soon as the diagnosis is made, therapeutic interventions such as occupational therapy, physical therapy, and speech and language therapy should begin, as well as medical interventions such as nutritional counseling and recombinant human growth hormone medication which can improve muscle tone, reduce developmental delays, improve short stature, and help manage excessive weight gain.

The mainstay for diagnosing PWS is a DNA Methylation Test which is the only test that will diagnose PWS caused by all three genetic mechanisms or subtypes: paternal deletion, maternal uniparental disomy (UPD), and imprinting center deletion. This test, also referred to as the “Prader-Willi/Angelman DNA methylation Panel”, detects more than 99% of affected individuals. DNA methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially in those who have atypical findings or are too young to show sufficient features to make the diagnosis on clinical grounds.

An oligo-SNP microarray will pick up the deletion class and size, as well as microdeletions that include the imprinting center and SNORD116, as well as 70% of uniparental disomy (UPD).

A FISH test (fluorescence in situ hybridization) will confirm a deletion on chromosome 15 if present, but will not reveal the size of the deletion nor the other two types of PWS, UPD or an imprinting center deletion, therefore it should not be used as the first genetic test.

If the DNA methylation test is positive, but the microarray or FISH test is normal, then the geneticist will need to do a DNA polymorphism analysis.

See GeneReviews for details of the PWS testing algorithm.

FAQs

Prader-Willi syndrome (pronounced PRAH-der WILL-ee) is a complex, rare genetic disorder that results from an abnormality on the 15th chromosome. Identified in 1956, it occurs in about one in 15,000 live births, in both males and females equally, and in all races.

Though Prader-Willi syndrome is a rare disease, it is one of the ten most common conditions seen in genetics clinics and is the most common genetic cause of obesity that has been identified.

PWS affects growth, metabolism, appetite, behavior, and overall development. Persons with PWS typically have weaker muscles, short stature if not treated with growth hormone, incomplete sexual development, and a chronic feeling of hunger that, coupled with a metabolism that utilizes drastically fewer calories than normal, can lead to excessive eating and life-threatening obesity. The drive to eat is never satisfied no matter how much food is consumed, necessitating constant and continuous supervision.

A blood test can confirm a diagnosis in most cases. If you suspect your child (or you) has Prader-Willi syndrome print the Diagnostic Criteria Sheet and mark the traits you have observed then discuss with your doctor. Consultation with a geneticist is recommended. Ideally you should start with a methylation test which detects approximately 99% of PWS cases. If the methylation test is positive you will then need either a FISH test or a PCR test to determine the sub-type, deletion or UPD respectively. There have been numerous instances when a negative FISH test results in a family being told their child does not have PWS only later (sometimes much later) to discover via a methylation or PCR test that their child has the UPD sub-type.

PWS is a lifelong, life-threatening condition, and there is no cure – yet.

Researchers continue to study Prader-Willi syndrome in hope of finding answers that could lead to effective treatments.

PWS is a randomly occurring genetic disruption that occurs at conception; there is no known cause for the genetic anomaly.  PWS is found in both males and females and across all races.

For more information about the genetics of PWS, please read GENETICS OF PWS.

There is no treatment for PWS as a whole, instead each symptom is “treated” or “managed”.  For example, many symptoms are improved through the use of growth hormone therapy.  Behavior therapy help manage the behavioral aspects of the syndrome, and proper Food Security helps manage weight.

Unfortunately, currently there is no effective treatment for the hyperphagia (excessive appetite) of PWS which is a hallmark symptom of the syndrome.  However, there are current research studies which may lead to a treatment for this symptom.

PWS is estimated to occur once in every 12,000 – 15,000 people.  As such it is a rare disease, however it is the most common genetic cause of obesity.

PWS occurs in both males and females and across all races.

Yes, the National Institutes for Health defines a rare disease as one that affects less than 200,000 people in the United States.

Given the incident rate of one in every 12,000 – 15,000 people there are approximately 20,000 – 25,000 people in the United States who have PWS. Unfortunately approximately 65% of these are not known to the national organization (PWSA-USA) and therefore are probably not receiving necessary support and services.

No – While there is a genetic disposition toward obesity, due to the combination of an insatiable appetite (hyperphagia) and an extremely low metabolism, with good food management by the parents or caregivers (individuals with PWS cannot be relied on to manage their own food intake) and regular physical activity, a healthy weight can be maintained.

Early diagnosis and growth hormone therapy has also helped prevent many children from becoming obese at a young age (as was almost certain in prior generations); this often leads to a healthier weight in adulthood as well.

No, in fact most infants with PWS are diagnosed with failure to thrive. The global hypotonia (weak muscles) make early feeding extremely difficult.

As with most syndromes, PWS is a spectrum disorder so each individual is unique. There is no set age at which the hyperhpagia (excessive appetite) begins; no one knows what causes the onset. For some the onset is as young as 2 or 3, yet for others the onset is not until much later. It is important to note that proper food management is crucial regardless of when hyperphagia begins. Most people with PWS have extreme anxiety about food even if they are not actively seeking food.