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About Prader-Willi Syndrome

	PWS Stages & Characteristics	Diagnosis	Treatment

Prader-Willi syndrome (PWS), first identified in 1956 by Swiss doctors A. Prader, H. Willi and A. Labhart, is a rare complex non-inherited genetic disorder associated with an abnormality of chromosome 15. There are no known causes for the genetic defect that results in this lifelong, life-threatening condition. Symptoms associated with Prader-Willi syndrome (PWS) are believed to be caused in part by a defect in the hypothalamus, an important supervisory center in the brain that controls metabolism of fats and carbohydrates, sugar levels in the blood, body temperature, blood pressure, heartbeat, the expression of emotions, the regulation of the sleep-wake cycle, the development of muscle tone, and many more functions of the body. The hypothalamus is connected to the pituitary gland, often called the “master gland of the body” because all the other endocrine glands depend upon its stimulation. Prader-Willi syndrome impacts the function of the pituitary gland which controls the release of important hormones, including growth and sex hormones.

PWS is estimated to occur randomly in 1 in 12,000 to 15,000 people and is found in people of both sexes and all races. The two most common types of PWS, Deletion and Uniparental Disomy (UPD), are considered not to be inherited, however genetic testing is recommended regardless of type if more children are desired. PWS 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.

There are a number of characteristics shared by individuals with PWS. It is important to remember that Prader-Willi syndrome is a spectrum disorder - the degree of severity of symptoms varies from individual to individual, and not every individual will exhibit every symptom. The symptom of hyperphagia (insatiable appetite) is, however, shared by all individuals with PWS, though the degree of hyperphagia will vary.

In addition to hyperphagia, the other hallmark symptom of PWS is the tenuous hold on emotions and behavior. People with PWS are often easily frustrated, impulsive, quick to anger, rigid and concrete thinkers, and highly anxious.
Infants with Prader-Willi syndrome typically are born with extremely low muscle tone (hypotonia), fail to thrive, and require varying degrees of assistance in order to survive. Essential medical and therapeutic interventions for children with PWS include growth hormone therapy, occupational therapy, physical therapy, oral-motor and speech and language therapy, social skills therapy, optometric or ophthalmologic care, rigorous dental care, behavioral and sometimes psychiatric intervention, and special education services.

Beginning some time in childhood, the brain fails to regulate appetite normally. For a person with Prader-Willi syndrome there is a constant preoccupation with food accompanied by an unrelenting, overwhelming, overriding physiological drive to eat. Normal satiety (the feeling of fullness after eating) does not exist. The physiological drive to eat is so powerful that most individuals with Prader-Willi syndrome will go to great lengths to eat large quantities of food; many try to sneak food and some may even try to steal. Some people may eat food discarded in the trash or even non-edible items. Along with hyperphagia, the metabolic rate is about half what it should be. So individuals with Prader-Willi syndrome can gain an enormous amount of weight in a very short period of time. Prader-Willi syndrome is not an eating disorder; it is a physiological defect in the brain that causes myriad symptoms.

Stages of Symptom Presentation

FIRST STAGE - Failure to Thrive

Low birth weight and subsequent failure to thrive, severe muscle weakness (hypotonia) and delayed developmental milestones characterize the initial stage. Because of the weak, limp muscles, infants are often unable to nurse or suck and may require special feeding techniques. The milestones of lifting the head, sitting up, crawling, walking, and speech tend to be delayed. On average, without synthetic growth hormone treatment, independent sitting is achieved at around 12-13 months, walking at 24-30 months, and tricycle riding at 4 years. Without oral motor/speech therapy, the first words typically appear at around 21 months, with sentences around 3½ years.

SECOND STAGE - Hyperphagia

The next stage usually begins in toddlerhood when a preoccupation with food and a compulsion to eat begins. Life becomes dominated by a voracious appetite and an unrelenting drive for food. People with PWS do not experience normal satiety, a feeling of fullness after eating, and can eat a tremendous amount of food without feeling ill. Often there is an inability to vomit. In addition to the desire for food, there is rapid weight gain on relatively few calories. Thus, if not controlled, the individual with Prader-Willi syndrome will quickly become obese.

Fat tends to accumulate on the lower torso, the buttocks, hips, thighs, and abdomen. If a person with PWS gains unrestricted access to food the result can be deadly (GI perforation or stomach tissue necrosis). Uncontrolled obesity may lead to illnesses such as high blood pressure, respiratory difficulties, heart disease, diabetes and death.

CHARACTERISTICS

The characteristics listed below represent Prader-Willi syndrome’s impact upon the person who has not had the benefit of early intervention and appropriate treatment and management strategies. It is important to note that some of these symptoms and characteristics can be reduced or even eliminated with appropriate intervention.

Abnormal growth: PWS causes a defect in the production and/or utilization of human growth hormone. Unless treated with recombinant synthetic human growth hormone, persons with PWS are typically short in stature, have small hands and feet, a narrow forehead and other subtle dysmorphic facial features.

Hypotonia: Infants generally exhibit severe hypotonia (muscle weakness). Muscle tone improves as the child ages but individuals do not develop normal muscle strength.

Hyperphagia and abnormal caloric utilization: It is believed that hyperphagia (insatiable appetite) results from a defect in the hypothalamus, the part of the brain that regulates hunger, satiety, and the body’s metabolic rate. Persons with PWS experience a biochemical drive to eat; they always feel hungry. Metabolism is about half the normal rate therefore persons gain weight on considerably fewer calories than the normal population.

Cognitive limitations: Central nervous system impairment results in IQs ranging from 40 to above 100. Almost all individuals, however, function in the mildly mentally retarded range independent of tested IQ. Most individuals will also be diagnosed with a general learning disability and some with Non-Verbal Learning Disorder.

Temperament and behavior issues: Young children with PWS tend to be loving, happy and compliant. Over time due to biochemical changes in the brain, subtle changes in mood may occur leading the child to become more easily frustrated, prone to mood swings, temper outbursts, stubbornness, rigidity, argumentativeness, have obsessive or compulsive thoughts and behaviors. Persons with PWS may experience an increased rate of psychiatric problems.

Speech and language problems: The extent of hypotonia as well as cognitive capacity affects speech problems. Apraxia of Speech, also called “dyspraxia” is common in individual with PWS. Oral-motor therapy in infancy and therapy targeted to treat Speech Dyspraxia are recommended

High pain threshold and irregularities in body temperature control mechanisms: Most persons with PWS are unaware of injury and infection because of blunted sensory mechanisms. The body’s ability to regulate internal body temperature is often impaired.

Skin scratching and picking: Persons with PWS often pick and scratch at sores and insect bites which, if not controlled, may result in infection.

Dental problems: PWS causes low saliva production which can result in thick, sticky saliva, soft tooth enamel, cavities, and gum disease. Products designed to treat dry mouth can improve or eliminate these symptoms.

Incomplete sexual development: Babies are typically born with small genitalia, and male babies are typically born with undescended testes. Without sex hormone treatment, most individuals do not produce sufficient sex hormones to allow them to progress through puberty.

Respiratory issues: Respiratory problems, including obstructive and central sleep apnea, can increase excessive daytime sleepiness, increase irritability, and exacerbate behavior problems.

Strength, balance and coordination: Along with the physical challenges associated with hypotonia, underdeveloped vestibular and proprioceptive systems often result in poor balance and coordination. Occupational and physical therapy are helpful to improve balance, coordination and strength.

Social isolation: Difficulties with social skills acquisition may lead to social isolation. Early Intervention programs should include social skills therapy. Individuals with higher levels of cognitive function may be more aware of their differences or limitations, which can lead to increased levels of depression. Counseling and medication may be helpful to treat the depression which may result in later years if self-image issues emerge over the conflict between independence and the need for management.

Other characteristics: Scoliosis; disordered sleep; gastrointestinal problems including reflux, slow moving bowel, delayed stomach emptying (gastroparesis); sensitivity to medications, especially anesthesia; eye abnormalities including strabismus (crossed eyes), myopia (nearsightedness), or amblyopia (lazy eye).