Prader Willi Syndrome

Updated April 24, 2019

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A list of references is also included at the bottom of this article.

What is Prader Willi Syndrome?

Prader-Willi Syndrome, also known as PWS, is a rare and complex genetic disorder that affects multiple body systems.

Prader-Willi Syndrome (PWS) is a genetic disorder related to a complex change on chromosome 15. It's very rare, only occurring in 1 in 10,000 to 15,000 people, 1though it’s possible that there are more cases that have gone undiagnosed.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

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Common traits include low muscle tone, small feet and hands, a small stature, intellectual disability, behavioral problems, delayed puberty and an uncontrollable appetite that can lead to childhood obesity. 2

Who Does Prader-Willi Syndrome Typically Affect?

PWS syndrome appears to be equally common among males and females, without increased rates in any specific ethnicities or backgrounds. 3

What are the Symptoms of Prader-Willi Syndrome?

There are a number of characteristic traits of PWS that can allow a pediatrician or geneticist to initially suspect or recognize the condition.

The most common initial symptoms of PWS in a newborn are related to activity and movement. Newborns with PWS will be lethargic, have poor muscle control, a weak cry, and poor reflexes.

It’s also quite common to note feeding difficulties because newborns will have a hard time sucking. As a result they may not gain weight properly, and overall exhibit a failure to thrive, despite having a normal birthweight. 4

Certain facial features can also aid in identifying children who have PWS. These include: 5, 6

  • Almond-shaped eyes
  • Crossed eyes, or eyes that don’t align properly when looking at an object
  • A thin upper lip
  • Downturned corners of the mouth
  • Lighter patches of hair, eyes, and skin compared to other family members
  • Crowded teeth

Once entering early childhood, the symptoms and behaviors may start to change and evolve. Most noticeably children will become very interested in eating large amounts of food, typically starting between the ages of 1 to 6.

They tend to seek out food to such an extent that they may become obese. This is believed to be the result of hormone imbalances that essentially take away the ability to feel satisfied after eating. 7

There will also be delays in hitting physical milestones and speech delays. Despite physical delays, overall activity tends to improve as a child grows, compared to the newborn period. 8

Other symptoms starting in the early childhood timeframe include: 9, 10, 11, 12

  • Not sitting unassisted until age 12 months
  • Walking at age 24 months
  • First words at 18 months, or as late as 6 years
  • Temper tantrums
  • Obsessive-compulsive behaviors
  • Manipulative actions such as lying or stealing food
  • High pain threshold
  • Lack of strength
  • Sleep disturbances
  • Skin-picking 
  • Short height
  • No growth spurts
  • Small hands and feet
  • Incomplete or delayed puberty

What Causes Prader-Willi Syndrome?

In about 75 percent of the confirmed cases of Prader-Willi Syndrome, people are missing a segment of chromosome 15. 13

The underlying cause in PWS is related to specific genes that are activated differently depending on which parent passed downthe gene.

There is a specific region on chromosome 15 that we know to be causative of PWS. When correctly expressed, the active copy of this gene is the one received from a father. We still have a copy from our mother, but the gene is essentially silenced.

In PWS, something has occurred to make the gene from the father silent, or the gene could be missing entirely. This means that along with the silent copy from the mother, the father’s copy is also silent or not present.

PWS patients are now entirely missing the genetic instructions that would have been provided from that gene.  

The main gene involved is called SNRPN. The product of this gene is found primarily in the heart and the brain, but can be found in many other tissues in the body. 14 

This gene is only able to work as intended when it’s present on the paternal copy of chromosome 15. In most circumstances, we have machinery in our cells that “reads” a gene and creates proteins that our bodies need.

On the maternal copy, the SNRPN gene is structured in such a way that the machinery can’t physically access the gene, and therefore it can’t make the protein we need. 

Most cases (75%) of PWS occur when the paternal copy is missing, or deleted, from chromosome 15. 15

Most other cases (20%) of PWS are caused when a child inherits two maternal copies rather than one from each parent. 16 This is known as maternal uniparental disomy, or UPD. 

The least common finding (5%) is a breakage or structural change in chromosome 15 that interrupts the intended gene function. 17


Is Prader-Willi Syndrome Passed Down Through Families?

For the most part, no. In most cases when a child is born with PWS it has happened as a result of a random change, and not something that the parents carried in their DNA.

Can Prader-Willi Syndrome Be Prevented?

There is no way to prevent a random genetic event like PWS.

If I Have a Child With Prader-Willi Syndrome, What Are the Chances That Future Children Will Have it as Well?

Just because parents already have a child with PWS doesn't necessarily mean that the next child will have it.

Since PWS usually occurs due to a random genetic event, there isn’t a high risk of this happening multiple times in the same family.

However, there does seem to be certain types of genetic changes that are more likely to run in families. One study reports that as of 2018 there have been 13 families reported who have more than one child with PWS. 18

In general, the risk of having multiple affected children is very low. Studies vary on what they find the risk to be, and it ranges from 0.1% 19 to 1.6%. 20

Can People With Prader-Willi Syndrome Have Children in the Future?

One of the effects of PWS is infertility due to the hormone dysregulation that occurs during growth and development. There appear to be only 2 reports of female patients with PWS having children of their own. 21

Diagnosis of Prader-Willi Syndrome

Newborns or young children generally first present to a pediatrician with the symptoms described earlier.

The biggest red flag for PWS tends to be the symptoms around lethargy and poor muscle control. 

How Do You Diagnose Prader-Willi Syndrome?

Testing for PWS could be suggested based on a thorough review of the patient’s symptoms and physical examination. Certain genetic tests are used to confirm a suspected case of PWS.

How Do Doctors Test for Prader Willi Syndrome?

A structured approach to testing for PWS is recommended to help make sure children aren’t subjected to any unnecessary tests. 

One test commonly used is a DNA methylation test. 22 This test looks at the SNRPN gene involved on chromosome 15 to see which parent the gene came from. Since PWS occurs if the copy from the child’s father is missing, the test can tell us if only a copy from the child’s mother is present.

If the test finds only maternal copies of the gene, that indicates PWS. Understanding the results of a DNA methylation test can be complicated and requires a genetics doctor.

A genetic counselor can help explain the results and what the results mean for future pregnancies or children.

Even with the result of the methylation test, that doesn’t specifically tell a doctor if the paternal copy of SNRPN is present but simply inactive, or if it’s missing due to a deletion. A FISH test can allow visualization of whether or not the gene is actually present on chromosome 15.

15 FISH is an acronym for Fluorescence in situ hybridization, which is a fancy way of saying that we have connected fluorescent tags onto the DNA in order to make it easier to see the genetic material of interest.  

Another technique, multiplex ligation-dependent probe amplification (MLPA) also both detects a missing segment of DNA and assesses the methylation pattern, identifying which parent passed down the material.

Other tests can be used to check for a gene deletion, such as a chromosome microarray, or a high resolution chromosome analysis. 23

Where are DNA Tests for Prader-Willi Syndrome Available?

Only your child’s pediatrician or other medical professional can order a DNA test for PWS. This is not a condition that you will see as part of an at-home DNA test.

Testing for Prader-Willi Syndrome Before Birth

During pregnancy, a low level of fetal movement or abnormal fetal heart rate may indicate PWS. 24 However these symptoms aren’t specific to PWS and could have various other causes, and so if there are any concerns during a pregnancy it’s essential to stay in close contact with your doctor.

It’s unlikely that symptoms during a pregnancy would lead to prenatal testing specifically for PWS, but it is possible to identify SNRPN deletions on a genetic test done prenatally.

There are two diagnostic methods available for prenatal testing: amniocentesis and chorionic villus sampling (CVS). Both involve extracting fluid or tissue from the uterus and carry a small risk to the pregnancy.

However, they can provide answers and help you prepare for the future.

Non-invasive prenatal screening (NIPS) offers a different approach to assessing risk for PWS in a pregnancy. NIPS uses a blood draw from the mother, eliminating direct risk to the fetus. NIPS is a screen, meaning the results provide a risk figure and are not diagnostic.

These results can tell you whether your pregnancy is at a low risk or an elevated risk to be affected by PWS. At least one laboratory currently offers a NIPS panel that includes evaluation of PWS. 25

A prenatal genetic counselor can help explain testing options related to high risk pregnancies and provide education and proper consent before any type of genetic test is ordered.

Prader-Willi Syndrome Treatment Options

Due to the many varied impacts of PWS on a patient, there are a number of approaches to treatment.

Personal Development

Physical therapy, occupational therapy and speech therapy should be started early to avoid patients falling far behind important milestones. These types of interventions can continue throughout school age years and beyond. 26

Hormone Therapy

Some growth hormones can help patients reach a height more expected of their age. They can decrease the fat-to-muscle ratio and decrease the amount of fat present overall, giving a leaner body.

This can have a positive impact on a younger child’s ability to meet motor milestones. 27, 28. Hormone therapy can be started on an infant or at the time of diagnosis. Working closely with a pediatric endocrinologist will be necessary to set up proper dosing and monitoring.

Sex hormone therapy can be used to help a child develop secondary sexual characteristics that can be impacted by the delay or absence of puberty seen commonly in PWS. 

Behavioral Treatments

Negative or disruptive behaviors can be treated both through a parent’s actions and through medications. Knowing how to properly manage the behavior issues seen with PWS can be hard on a parent, and seeking professional counseling or assistance can be helpful.

Remaining firm and consistent with a child is important to reinforce expected behaviors. 29 A class of medications that has been shown to be effective in managing behaviors are selective serotonin reuptake inhibitors, or SSRIs. 30

It’s important to work closely with your child’s doctor to determine the most appropriate dose of any medication because a study has shown that children with PWS tend to be more easily affected by certain medications than other children. 31

Dietary and Nutrition

Managing the desire for food in PWS children can make it extremely difficult to maintain a healthy weight and lifestyle overall. There are no medications that have shown to be effective for managing this, so maintaining a healthy diet and getting regular exercise are the best recommendations.

It’s even seen that children with PWS may have a lower daily caloric need than other children, making it even more difficult to maintain a balanced diet. 32

Keeping an eye on height, weight and BMI, along with daily monitoring of food intake is recommended.

The Prognosis for Prader-Willi Syndrome

Early detection of the genetic disorder is essential in maintaining a better quality of life. 

The impact of having a high BMI can cause other complications for patients with PWS. If not managed properly, these complications can lead to a reduced life expectancy. However, with appropriate interventions and treatment, patients should be expected to live a normal lifespan. 33

Living in a group home targeted specifically at PWS during adulthood can be beneficial for some patients. 34

Is There a Cure for Prader-Willi Syndrome?

There is no cure at this time for PWS. Managing symptoms and avoiding complications will help allow patients to have a full and healthy life.

Where can I get support if my family is affected by Prader-Willi Syndrome?

Talking with other families and experts in PWS can provide much needed guidance as you navigate this complex condition. Don’t be afraid to reach out for help from other people who have walked this path already.

Below are several organizations and advocacy groups involved in sharing knowledge and promoting research for PWS.

Referenced Sources

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