Medically reviewed by Daniel Combs, MD

• Clinical signs raise suspicion for Prader-Willi syndrome (PWS), but genetic testing confirms it.
• Signs vary from low muscle tone and feeding problems in babies to hunger that can’t be satisfied and obesity in early childhood.
• A type of genetic testing called DNA methylation testing detects over 99% of cases of PWS.

Healthcare providers diagnose Prader-Willi syndrome (PWS) using a combination of clinical signs and genetic testing. If someone has several symptoms of PWS, they can be sent for genetic testing to confirm the diagnosis and determine which subset of the disease they have.

Symptoms That May Prompt Genetic Testing

Healthcare providers use a scoring system to decide if someone needs genetic testing for Prader-Willi syndrome. PWS symptoms are grouped into major and minor criteria. The person must have a certain number of symptoms from each category for it to be considered a potential case of PWS.

• Children younger than 3: At least four major criteria and at least one minor criterion
• People older than 3: At least five major criteria and at least three minor criteria

The following symptoms may also support a PWS diagnosis:

• Bone problems 
• Crossed eyes
• High pain tolerance or inability to vomit 
• Temperature regulation problems

Genetic Testing

Your DNA is organized into chromosomes. You have 23 pairs of chromosomes, for a total of 46. With Prader-Willi syndrome, part of chromosome 15 from your father is missing or not working. Genetic testing for PWS focuses on this chromosome. 

Types of Genetic Testing

DNA methylation is a blood test that checks if certain genes on chromosome 15 are missing or turned off. It confirms PWS with over 99% accuracy and detects all three PWS subtypes.

Once DNA methylation confirms the diagnosis, fluorescence in situ hybridization (FISH) and chromosomal microarray tests determine subtypes. Because each test can miss certain subtypes, a negative FISH or microarray result alone cannot rule out PWS—DNA methylation is always needed.

Subtypes of Prader-Willi Syndrome

PWS subtypes include:

• Paternal deletion (60% of cases): A piece of the paternal chromosome is missing. It typically involves more characteristic physical traits.
• Maternal uniparental disomy (35% of cases): You inherit two copies of chromosome 15 from your mother and none from your father. Diagnosis often occurs later because it causes fewer classic physical symptoms.
• Imprinting defect (in less than 5% of cases): Your paternal genes are present but do not function properly. 

Is PWS Hereditary?

Most cases of PWS are random and not inherited. The chance of having another child with PWS is less than 1%. However, in rare cases of an imprinting defect, the risk increases to 50%. 

When Is Prader-Willi Syndrome Usually Diagnosed?

Most diagnoses occur within the first two months of life. But it can occur later, depending on access to testing and which signs appear first. 

Before Birth

Prenatal diagnosis is less common. If you have a family history or there is reduced fetal movement or extra amniotic fluid, you may have an amniocentesis. This is a diagnostic test done during pregnancy to check the fetus for genetic disorders, which may reveal PWS. 

Infancy (0–24 Months)

Healthcare providers suspect PWS when a baby has hypotonia (low muscle tone) with a floppy appearance. About 97% of newborns with PWS have this symptom. They may also suspect the condition if your baby has trouble feeding, struggles to gain weight, or needs a feeding tube.

Some babies show more typical growth between 9-24 months, which can make it seem like symptoms are improving. This shift can delay diagnosis before later changes in appetite and weight appear.

Early Childhood (Ages 2–8)

As your little one grows, signs change from feeding problems to extreme hunger, developmental delays, weight gain, and behavioral concerns.

You may notice:

• Extreme hunger and food-seeking behaviors 
• Delayed walking or talking 
• Learning challenges
• Skin picking or self-inflicted injuries
• Temper tantrums or emotional outbursts
• Rigid thinking
• Sleep problems
• Weight gain

Children who don’t get a diagnosis as an infant often receive one during this stage, with an average age of around 4 years.

Older Children, Adolescents, and Adults (8+ Years)

Weight gain, behavioral concerns, and developmental challenges continue into later childhood and teenage years. Delayed puberty is also a common symptom. 

Diagnosis in adulthood is less common but can happen, often after years of infertility, obesity, or mental health concerns.

Is It Possible To Be Misdiagnosed?

Prader-Willi syndrome can be missed because: 

• Babies may receive a general diagnosis like failure to thrive without genetic testing
• FISH or microarray tests can miss some types of PWS without DNA methylation
• Symptoms change, and providers may only see one phase

Some conditions can also look similar. For example, Angelman syndrome affects the same chromosome but involves the mother’s genes instead of the father’s. Genetic testing helps tell the conditions apart.

Other conditions can cause similar symptoms, too. For example:

• Meltdowns may overlap with attention-deficit/hyperactivity disorder (ADHD) or autism
• Skin picking can occur with obsessive-compulsive disorder (OCD)
• Weight gain may be due to hypothyroidism (underactive thyroid)

Next Steps

If you suspect a loved one has Prader-Willi syndrome, explain the signs and patterns you see to a healthcare provider and ask about genetic testing. If they receive a diagnosis, ask about early treatment and the specialists needed to manage the condition. The sooner a multidisciplinary care team is in place and treatment begins, the better the long-term outlook. Also consider connecting with support organizations like the Foundation for Prader-Willi Research. 

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Kristina Dawson