Prader-Willi Syndrome (PWS) is a genetic disorder characterized by neurological impairments causing an
unusual pattern of growth and development related to an abnormally increased appetite with an excessive
need for food consumption. Prader-Willi Syndrome affects 1:12,000 -15,000 live births and is found in both
genders and all races.
Physical characteristics of PWS include short stature, small hands and feet, and a characteristic facial
appearance consisting of a thin upper-lip, down-turned mouth, dental crowding, and almond shaped eyes.
Developmental milestones are delayed, and learning disabilities are always present, but may vary in severity.
Behavioral problems include temper tantrums, obsessive compulsive tendencies, and skin-picking. Its
characteristics also include loss of muscular strength, uncontrolled appetite, obesity, delayed pubescence;
variable degrees of mental retardation or functional retardation. Sexual development may occur early or late,
but it is usually incomplete. Individuals with PWS do not undergo spontaneous pubertal development and are
infertile.
The stress on families is often immense. The constant pressure of food control and behavior management
affects all family members, such as higher divorce rates and siblings with emotional problems. The child
with PWS can become a dictator who rules the family and, with age, becomes more difficult to handle.
Recognition of the strains and dealing with them early on is essential to the family’s vitality.
Areas of Development
Children with Prader-Willi show developmental delays in all areas typically by one to two years behind
children of the same age. For example, walking usually occurs at about age two. Gross motor and balance
are difficult skills for them to master but are goals that slowly but surely will be achieved. Speech and
language difficulty is common, although the cause is not quite clear. Speech therapy is beneficial to ease the
frustration with any communication deficiency. Though language development is delayed, verbal ability is
often a strong. However, articulation may remain weak. Logical thinking and concepts (the idea of putting a
plan into effect) are impaired. The average IQ is around 70, with a range from 40 to 105. Even with a lower
IQ, cleverness in finding food can occur.
Behavioral problems, ranging from stubbornness to violent temper tantrums which increase with age, usually
begin to appear during the preschool years. Other common characteristics include a high pain threshold,
dental problems, and breathing difficulties. Medical intervention therapy can be used to modify the severity
of violent tantrums (e.g., fluexitine serotonin uptake inhibitors have been helpful in some cases). Other
conditions such as depression and psychotic episodes have been reported. Medications in most cases have
not been found generally useful in controlling appetite. Drug treatment is essential at times but is not
recommended for permanent use. Consult the national PWSA office or speak with your child’s physician for
updates and information.
Motor skills like sports activities are limited. Running and jumping can cause joint injuries due to poor
muscle strength and coordination. There are occurrences of bone fracture, possibly related to fragile bones
and decreased muscle mass. Adaptive physical exercise is necessary during school years. Walking,
swimming, and stationary exercise equipment are recommended. Most cases of children with Prader-Willi
syndrome become apparent to parents and physicians because of their motor development (poor muscle
tone), developmental delay, and/or obesity as infants.
Adults with PWS can function well in assisted living facilities with adequate control over food intake and a
structured living setting. Their difficult personalities and explosive tempers make supervision and counseling
hard. Adults may lead a productive life in a group setting with opportunity in light industrial workshops
which offer the best employment possibilities.
Weight Control and Obesity
Obsessive eating and a fixation with food usually begin between the ages of 2 to 4, although it may present
later on. Some children learn to eat at set times and may refuse certain foods, but the craving for food in
general will always persist. Sneaking or stealing extra food is typical. In most situations, all sources of food
must be kept under lock and key. This may involve uncommon discipline such as locking the refrigerator or
kitchen cabinets. Avoid purchasing foods that are tempting and fattening.
Obesity occurs in 95% of cases if there is no supervision over the amount of food absorption. About two-
thirds of individuals cannot vomit even after consumption of spoiled food or other foul substances. An
increasing number of children with PWS are being diagnosed before an onset of obesity. Whether obese at
diagnosis or not, more and more have their weight managed within acceptable numbers. Calculation of
calories and exercise are critical to weight control and obesity.
Possible Causes
The first patients with characteristics of Prader-Willi Syndrome were described by Dr. Prader, Dr. Willi, and
Dr. Lambert in 1956. Initially, scientists found that individuals with PWS have a region of genetic matter
deleted (erased) from chromosome 15. In order to have PWS, the genetic matter must be deleted from the
chromosome 15 received from one's father. If the deletion is on the chromosome 15 inherited from one's
mother a different syndrome develops. This important discovery proved for the first time that the genes
inherited from one's mother can be perceived differently than the genes inherited from one's father.
As more cases emerged scientist concluded that some individuals with PWS did not have deleted genetic
matter from chromosome 15. Further studies found that these patients inherit both copies of chromosome
15 from their mother. This is not typical. Normally, an individual receives one chromosome 15 from their
father and one chromosome 15 from their mother. When a person receives both chromosomes from the
same parent it is called "uniparental disomy” (UPD).
Scientists are still discovering other causes of PWS. A small number of patients with PWS have a change
(mutation) in the genetic matter on the chromosome 15 inherited from their father. This mutation prevents
certain genes on chromosome 15 from working properly. PWS develops when these genes do not work
regularly.
Prader-Willi syndrome is caused by a deficiency in the crucial area of chromosome 15. Nearly 70% have an
imperfection and other abnormal findings in chromosome 15, which is detected by using high resolution cell
and chromosome analysis. PWS is an impressionable disorder caused by a faulty connection in the paternal
copy of chromosome15. There is a 50% chance of having more than one child with the disorder; it all
depends on gene formation.
Making a Diagnosis
During infancy the diagnosis of PWS may be noticeable due to poor muscle tone, feeding problems, small
genitalia, or the unique facial features are present. If an infant has these features, testing for PWS should be
performed. This testing should also be offered to children and adults who display features commonly seen in
PWS (developmental delay, uncontrollable appetite, small genitalia, etc.). There are several different genetic
tests that can detect PWS. All of these tests can be performed from a blood sample.
Methylation testing detects 99% of the cases of PWS. Methylation testing can detect the absence of the
paternal genes that should be normally active on chromosome 15. Although methylation testing can
accurately diagnose PWS, it can not determine if the PWS is caused by a deletion, maternal uniparental
disomy (UPD), or a mutation that disrupts imprinting. This information is important for genetic counseling.
Therefore, additional testing should be performed.
PWS can be detected before birth if the mother undergoes amniocentesis testing or chorionic villus sampling
(CVS). This testing is only recommended if the mother or father is known to have a chromosome
rearrangement, or if they already have a child with PWS syndrome.
Treatment
At this time there is no cure for PWS. Early interventions like physical therapy help improve muscle tone.
Some infants with PWS also require special nipples and feeding techniques to improve weight gain.
Treatment and management during childhood, adolescence, and adulthood is generally focused on weight
control. Strict control of food intake is necessary to prevent obesity. A lifelong restricted calorie diet and a
regular exercise program are also advised. Unfortunately, diet medications have not been shown to
significantly prevent obesity in PWS. However, growth hormone therapy has been shown to improve the
poor muscle tone and reduced height typically associated with PWS.
Special education may be helpful in treating developmental delays and behavior problems. Individuals with
PWS typically excel in highly structured environments. Early intervention with a dietitian and behavioral
psychologist to prevent excessive weight gain in childhood is important. With appropriate interventions and
ongoing support, people with Prader-Willi Syndrome live a normal life expectancy. Most adults live with
family or in accommodation with various interventions.