What is Prader-Willi Syndrome (PWS)?

Prader-Willi Syndrome (PWS) is a rare and complex genetic disorder that results from an abnormality on chromosome 15. It affects approximately 1 out of every 15,000 to 30,000 people, and occurs in both males and females, as well as across different races and ethnicities with equal frequency. PWS is recognized as the most common genetic cause of life-threatening childhood obesity.

PWS affects a person’s appetite, growth, metabolism, cognitive function, and behaviour. The hallmark characteristics of PWS are chronic feelings of insatiable hunger (hyperphagia), low muscle tone (hypotonia), and a slowed metabolism that can lead to excessive eating and life-threatening obesity.

Prader-Willi Syndrome (PWS) occurs because of an abnormality on the 15th chromosome. This can happen in one of three ways:

Deletion: Occurs when critical genes in chromosome 15 inherited by the father are missing or deleted. This is the most common cause of PWS and occurs in approximately 60% of cases of PWS.

Uniparental Disomy (UPD): Occurs when two copies of the mother's chromosome 15 are passed down rather than one from each parent. This occurs in approximately 35% of cases of PWS.

Imprinting Defect: Occurs when there's an imprinting mutation on the father's chromosome 15 where the genetic material is present, but inactive. This occurs in less than 5% of cases of PWS. In these cases, PWS can reoccur within a family.

Prader-Willi Syndrome (PWS) causes a dysfunction in the portion of the brain called the hypothalamus which plays a crucial role in regulating many bodily functions, including hunger, emotions, pain, body temperature, sleep, fluid balance, puberty and fertility.

Some common characteristics that individuals with PWS may have are:

Hyperphagia (lack of satiety/constant feeling of hunger)
Developmental delays and cognitive challenges
Hypotonia (low muscle tone, poor growth and physical development)
Behaviour and mental health concerns
Growth hormone deficiency and short stature
Low metabolism and rapid weight gain
High pain tolerance
Skin picking
Speech problems
Sleep disturbances
Underdeveloped sex organs

It is important to note that the appearance and severity of these symptoms/characteristics may change over time and can vary from person to person.

Stages of Development and the Appearance Symptoms/Characteristics of PWS

Early Life

At birth, some symptoms of Prader-Willi Syndrome may be noticeable:

Infants have low muscle tone and appear quite floppy
Poor sucking reflex and feeding difficulties that often require special assistance
Distinct facial features like almond-shaped eyes and a narrowing at the temple

Childhood

Throughout toddler and childhood years, there is a shift in PWS symptoms.

Increased interest in food and insatiable hunger that can lead to weight gain if not properly managed.
Children with PWS may be slower to meet their developmental milestones, and may have mild to moderate intellectual impairment.
Behavioural issues such as temper tantrums, compulsive behaviours, resistance to change, and stubbornness may become more prevalent.

Teenage Years

In the teenage years, more challenges tend to arise in PWS symptoms.

Delayed or incomplete physical development that impacts puberty, overall body composition.
May experience difficulty in connecting with peers and interacting socially.
Continue to experience hyperphagia.
May struggle with change, so transitions from elementary school to high school, and from out of high school can be difficult.

Adulthood

New challenges tend to arise as individuals with PWS become adults.

Mental health concerns such as depression, anxiety, psychosis may develop.
Orthopedic issues such as scoliosis may develop or worsen.
May experience endocrine issues like diabetes or low sex hormone levels.

Although not always, these days it is more common for babies born with Prader-Willi Syndrome (PWS) to be diagnosed within a few months of birth.

Newborns with PWS have hypotonia (low muscle tone) and are quite floppy. They also have a poor sucking ability so experience failure to thrive because they have problems with feeding and tend to require feeding tubes. Newborns with PWS may also exhibit characteristic facial features such as almond-shaped eyes. When these symptoms present themselves, a health care provider will likely conduct genetic testing for PWS.

Some individuals with PWS may not be diagnosed at birth or may be misdiagnosed, and only later diagnosed with PWS when other symptoms become more prevalent.

PWS is diagnosed through a series of specialized genetic tests that involve samples of blood and saliva. The preferred method of testing is DNA Methylation Testing which detects over 99% of PWS cases and checks for all three genetic subtypes. A FISH (fluorescence in-situ hybridization) test identifies PWS by deletion, however, it cannot detect other forms of PWS. Blood may be drawn from the parents in cases where PWS by imprinting defect is suspected.

In PWS by imprinting defect cases, PWS does have a chance of recurrence in the family. Families with concerns about their risk of recurrence should speak with a genetic counselor.

While there is no cure for PWS, there are several treatments available for individuals with PWS to aid with physical and intellectual development. In order to decide the best course of action for you and your child or family member with PWS, consult your general practitioner or other doctors who specialize in researching and treating PWS.

Human Growth Hormone (HGH): Most individuals with PWS are growth hormone deficient. Administering human growth hormone (or HGH) to individuals with PWS has been proven to be beneficial to their health as it both increases height, improves body composition, and increases energy and physical activity.

Behavioural Therapy: Individuals with PWS often experience behavioural issues such as difficulty expressing and controlling emotions, therefore many families have found behavioural therapy beneficial in helping individuals with PWS express, control, and understand their emotions.

Physical Therapy and Occupational Therapy: Individuals with PWS can benefit from physical therapy and occupational therapy in order to improve their gross and fine motor skills.