Prader-Willi syndrome is a complex neurobehavioral genetic disorder resulting in low uscle tone, incomplete sexual development, hyperphagia and poor metabolic function. Other factors that may cause difficulties include adverse reactions to medications, high pain tolerance, gastro-intestinal and respiratory issues. Severe medical complications can develop rapidly in individuals with PWS.

Some key medical issues are in our booklet MEDICAL ALERTS for parents and professionals. Please call (800) 926 - 4797 to request a hard copy of this booklet.


 

A – F

Central Adrenal InsufficiencPersons with PWS often have deficiencies of the pituitary hormones. The pituitary controls the adrenal gland, which is the source of cortisol. Cortisol an essential stress hormone which may be adequate in health, but during illness. Symptoms are subtle but may include exhaustion during illness and slow recovery. ACTH/ Central Adrenal Insufficiency should be considered in person with PWS; current research (2017) is not conclusive.

 

Central Adrenal Insufficiency

 

“Adrenarche” is the term for the development of sexual hair – underarms, genital, and facial hair. In childhood, this hair growth is the result of hormones (testosterone) made by the adrenal gland, and it is not true puberty, which occurs when the ovary or testes begin to make hormones. This system activates before real puberty, often at age 8 or 9 years. In children with PWS, this system can activate even earlier, for unknown reasons. Children may experience some growth of underarm hair at age 6 or 7 years. This does not mean true puberty will come early.

People with PWS may have unusual reactions to standard dosages of medications and anesthetic agents. Use extreme caution in giving medications that may cause sedation and suppress breathing: prolonged and exaggerated responses have been reported. Many individuals with PWS require overnight observation for typically outpatient procedures due to slow clearance of anesthesia and the added effects of pain medications. Slowed recovery of GI function should be considered as well, and very cautious and slow transition to drinking and eating is advised to delay obstruction.

Anesthesia and PWS

Anesthesia complications study

 

 

Respiratory health can be challenging because of the low muscle tone (muscles are needed for breathing) and sometimes impaired hypothalamic control of breathing. “Silent aspiration” is when fluids can enter the lungs rather than the stomach while drinking, due to abnormal swallowing patterns. Scoliosis and kyphosis can also impair chest expansion needed for healthy breathing.

Respiratory problems

Respiratory Review Pediatric

Preventing obesity is the best way to prevent heart complications. The most common heart condition in PWS is right heart failure due to significant obesity. One symptom is leg swelling which should prompt an urgent evaluation by a physician.

Poor muscles tone, thick saliva, and often uncoordinated swallowing muscles contribute to problems with swallowing. All family members and providers should be able to perform the Heimlich maneuver. No person with PWS should eat alone; even water can be difficult to swallow.  *See Swallowing

Subclinical Dysphagia

Bowel function is often impaired due to abnormal motility, poor muscle tone, and low metabolism. Lack of exercise contributes. Concerns about abnormal swallowing, bowel obstruction and motility function have shifted treatment away from a high fiber diet. Many individuals respond well to polyethelene glycol (Miralax) and/or scheduled toilet sitting.

Constipation in Children

GI Stomach and intestinal problems

 

Many of the dental problems with PWS are related to decreased saliva, and mouth breathing. Normal saliva is thin and washes the teeth clean, while the thick saliva associated with PWS sticks to the teeth and harbors bacteria that cause tooth decay and periodontal disease. Crowded arches contributes to misalignment of the teeth. Tooth wear, in terms of both erosion and attrition, is a severe problem in young adults with Prader-Willi syndrome. Fluoride needs are the same, not less, than other children.

Dental Problems

Dental Care

Very specific genetic testing is needed to make the diagnosis of PWS.  Prior to the development of this technology, the syndrome was diagnosed based on clincial findings.

TESTING AND DIAGNOSIS

 

There is no single diet that is best for all individuals with PWS.  Caloric intake should be determined with assistance from a dietitian or physician based on what is best for your child and family.  PWSA (USA) has a variety of age-specific nutrition guideline booklets for reference.  Meals and snacks should be carefully planned, rather than spontaneous and as a requested to manage both weight and food related anxiety.

 

Low muscle tone can affect eye muscle strength and many babies with PWS have difficulty coordinating their eyes (strabismus, sometimes called “lazy eye”). This needs to be closely monitored and evaluated by an ophthalmologist (MD). Vision can be permanently affected if this is not treated.

 

Individuals with PWS have higher rates of respiratory illnesses and must be protected. Influenza is not the same as “stomach flu”. It is a dangerous, life threatening respiratory infection with a significant death rate. It should be prevented through annual vaccination and hand washing.

Although GH has been mentioned to be contraindicated in cases of severe obesity and respiratory compromise, it does not mean that GH will worsen the symptoms of common respiratory illnesses. There is no evidence that stopping GH during respiratory illness would have any benefit.

CDC recommends influenza vaccine after 6 months of age especially in individuals at risk. All individuals with PWS would fit in the high risk category and should be vaccinated.
Synagis is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease such as infants with bronchopulmonary dysplasia (BPD), infants with a history of premature birth (≤35 weeks gestational age), and children with significant congenital heart disease.

Pneumonia is a broad term that covers many types of infections. All children are immunized for some pneumonias (HIB). There are immunizations for pneumonia given at age 65 years, and an immunization for pneumonia (Prevnar) given to people with specific risk factors; these do not include PWS.

Pneumonia vaccines

The hallmark of weight management is a concept called “Food Security”. Individuals with PWS will have improved physical and mental health if food is not obtained by chance, by request, or on demand. These are key principles in management. Kitchens often need to be locked to reassure the individual with PWS that they cannot obtain food; this leads to decreased anxiety and is not a punishment, but a tool for success.

Medical Necessity for Food Security Statement

Food Security-Locks and Alarms

 

G – K

Abdominal distention or bloating, pain, and/or vomiting (which is very rare in PWS) may be signs of life-threatening gastric inflammation or necrosis, more common in PWS than in the general population. Rather than localized pain, there may be a general feeling of unwellness. If an individual with PWS has these symptoms, close observation is needed. An X-ray and an endoscopy with biopsy may be necessary to determine degree of the problem and possible need for emergency surgery.

GI Stomach and intestinal problems

GI issues

GI Gastroparesis

GI Algorithm Chart

 

Research on using growth hormone (GH) with Prader-Willi syndrome (PWS) began in 198I. In June 2000, growth hormone was approved by the U.S. Food & Drug Administration (FDA) for the treatment of growth failure in Prader-Willi syndrome. Since that time, extensive research has substantiated global benefits of this therapy, beyond its impact on height.

A hospital stay of any type can present unique challenges for the patient with Prader-Willi syndrome. It is crucial that all staff be aware of the need for strict food control and not allow the patient extra food or food items not on their approved diet plan. It is important that family members assume that staff have no previous experience with this rare syndrome.

Medical Alert - Routine or ER Treatment

Postoperative monitoring of patients

Postoperative monitoring of pediatric patients

If diet is not properly managed, obesity in PWS typically begins between two and four years of age.  As infants, there is almost an absense of appetite drive.  The appetite gradually increases in early childhood such that by about eight years of age teh individual with PWS is showing signs of an insatiable appetite (hyperphagia).  Through studies, seven distinct nutritional phases and subphases have been identified.  Currently, there is no FDA approved treatment for hpyerphagia; however, there are several drugs in various stages of clinical trials.

Nutritional Phases

 

Thyroid hormones are important to all cells in the body; thyroid is essential to maintaining a normal metabolism. The thyroid gland (located in the neck) is under the control of the pituitary gland (in the center of the brain), which in turn is regulated by the hypothalamus (region of the brain). Low thyroid function can be the result of the gland itself (either congenital or primary hypothyroidism); this is the most common and most severe type. All babies are tested after birth for congenital hypothyroidism. Less common and more difficult to diagnose is secondary or tertiary hypothyroidism – when the pituitary/hypothalamus do not fully stimulate the thyroid gland to make this important active hormone. It is this type of thyroid deficiency which is more likely in persons with PWS, rather than the type which is related to an inactive thyroid gland.

Thyroid Issues

 

Body temperature is under the control of the hypothalamus, so persons with PWS may have a normal temperature that is lower, or higher, than 98.6. Parents and caregivers should be aware of what is “normal” for their loved one. 94 degrees is considered dangerously low and requires immediate medical attention. Hypothermia may occur during minor illness and after receiving anesthesia. Fever may be absent despite serious infection.

Hypothermia

Hypothermia prevention

 

L – R

The lifespan for person with PWS has increased dramatically over the past decades as parents became empowered in optimal care of their children, preventing obesity and improving function through medications and therapies. Obesity issues cause the majority of deaths. Sudden unexpected deaths still occur. When a death occurs at any age or circumstances, PWSA offers counseling and support. We urge providers and parents to contact us when any death occurs in a person with PWS.

One of the ways researchers seek knowledge about the causes and possible treatments for Prader-Willi syndrome is through study of bodily tissue from individuals with the syndrome. Brain tissue, in particular, is critical to researchers who are trying to learn why PWS causes dysfunction in the hypothalamus portion of the brain.

Causes of Death

Even before birth, low muscle tone and muscle weakness are a hallmark of PWS. Growth hormone therapy improves muscle mass and muscle strength. Intensive physical therapy in infancy, and generally throughout childhood, are essential care. Children with PWS sit, crawl, and walk later than average. Low muscle mass is part of the explanation for low metabolism.

People with PWS may have unusual reactions to standard dosages of medications. Use extreme caution when prescribing or giving medications that may cause sedation (sleepiness). It is common for medications to be poorly metabolized and affect the person for a longer time than expected. “Start low, go slow” is the best advice when beginning a new medication. This does not apply to vaccinations which should be administered on the recommended schedule.

Medication combinations warning

 

Obesity prevention begins early in the toddler years by working closely with physicians and a dietitian to provide an individualized healthy caloric intake, food security and daily exercise.  PWS is the most common cause of genetic childhood obesity.  There is no PWS specific diet, however avoiding processed foods and added sugars is recommended.

  • Orthopedic Issues (HIP, SCOLIOSIS, KYPHOSIS)

    Children with PWS need recurrent evaluations with an orthopedic surgeon for the purpose of monitoring the known risks in PWS. With low muscle mass and muscle tone, there can be hip dysplasia(leg bone not completely positioned in the socket) at birth. Scoliosis (sideways curve of the spine) can occur in infancy and in later childhood. The incidence is not increased by the use of growth hormone. Some specialists use braces or casting to minimize the need for surgical correction. Kyphosis (hunched back) can occur later in childhood or adulthood. Osteoporosis is more common in PWS (see separate entry).

     

    Scoliosis monitoring

Many individuals with PWS have osteoporosis (low bone mineral density). This condition is most often diagnosed in adolescence and adulthood. The cause(s) of the osteoporosis is not known, but it is thought to be primarily due to the growth hormone and sex hormone deficiencies that occur in PWS. Low muscle tone and decreased exercise patterns may be contributing factors.

Osteoporosis consensus statement

 

Decreased pain signals and sensation are common in PWS. This may mask the presence of infection or injury; a person with PWS may continue to walk on a broken ankle, for example, or not complain of pain until an infection is severe. Persons with PWS may have difficulty describing pain, and just complain of not feeling well. Parent/caregiver reports of subtle changes in condition or behavior should be investigated for a medical cause, especially when abdominal pain is suspected.

There may be increased prevalence of poisoning in people with PWS compared to their non-PWS siblings. Several features of PWS, including the food-related behaviors (specifically ‘looking and searching for food’), decreased cognitive ability, eating unusual objects, and a history of extreme behaviors appear to correlate with this increased prevelance. Prescription, non-prescription drugs, alcohol and cleaning substances should be locked up. Spoiled foods should be disposed of carefully, and if the child or adult with PWS is an extreme food seeker, food pantries and refrigerators may need to be locked up.

When a person has ingested poison or other dangerous items, emetics are usually given to prompt vomitting; this may be ineffective in someone with PWS, and using this therapy first may delay lifesaving treatment.

 

Patients with Prader-Willi syndrome are known to have increased risks after surgery due to:

  • Apnea – high risk of central, obstructive, mixed apneas
  • Aspiration risk (motility abnormalities)
  • Decreased pain sensation
  • Deep vein thrombosis
  • Gastroparesis, gastric ileus, obstruction
  • Hypercapnia (excessive carbon dioxide in the blood) and hypoxia (deficiency in oxygen) – abnormal response
  • Hypotonia (low muscle tone)
  • Narrow oropharyngeal (airway) space
  • Obesity
  • Prolonged exaggerated response to sedatives
  • Scoliosis is common, with decreased pulmonary function
  • Thick secretions (saliva)

Medication combinations warning

Postoperative monitoring of pediatric patients

Postoperative monitoring of patients

Patients with Prader-Willi syndrome are known to have increased risks after surgery due to:

  • Apnea – high risk of central, obstructive, mixed apneas
  • Aspiration risk (motility abnormalities)
  • Decreased pain sensation
  • Deep vein thrombosis
  • Gastroparesis, gastric ileus, obstruction
  • Hypercapnia (excessive carbon dioxide in the blood) and hypoxia (deficiency in oxygen) – abnormal response
  • Hypotonia (low muscle tone)
  • Narrow oropharyngeal (airway) space
  • Obesity
  • Prolonged exaggerated response to sedatives
  • Scoliosis is common, with decreased pulmonary function
  • Thick secretions (saliva)

Medication combinations warning

Postoperative monitoring of pediatric patients

Postoperative monitoring of patients

Medical Journal Review and Summary

Abstracted by Kathy Clark RN MSN BC-CS, Medical Coordinator

 

Butler, MG. Benefits and limitations of prenatal screening for Prader-Willi syndrome. Prenat Diagn. 2017;37(1):81-94.

 

Petersen AK, Cheung SW, Smith JL, Bi W, Ward PA, Peacock S, Braxton A, Van Den Veyver IB, Breman AM. Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory. Am J Obstet Gynecol. 2017;217(6):691.e1-691.e6.

 

Prenatal testing for PWS (NIPT) is simple blood test from the mother sometimes recommended in early pregnancy to screen for genetic disorders in the fetus. Testing for microdeletions, a genetic problem in PWS, is technically more difficult than finding a missing or extra chromosome such as in trisomy 21 (Down syndrome), a much more common condition than PWS. Benefits and limitations of prenatal screening for PWS were recently reviewed by Dr. Butler in 2017. When NIPT technology first emerged, parents of children with PWS worried whether such information might lead couples to decide to terminate a pregnancy – amid the optimism of medical research and improved quality of life in our youngest generations, and their own valued experiences with a child with PWS.

 

There have been two previous studies describing experiences about this testing done at other centers. One center detected a single case of PWS prenatally, with a confirmed diagnosis of PWS using tests performed after birth. In a second study at a different center, 9 children were diagnosed prenatally with PWS, and all of them were confirmed to have PWS after birth. In a third study, there were 10 prenatal screening tests that were positive for PWS/Angelman syndrome, and yet none of these babies were diagnosed with either of these disorders after birth. This showed a dramatically different outcome than the first two studies indicating that NIPT has significant limitations when it comes to diagnosing microdeletions from DNA isolated from the developing fetus and found in the maternal blood sample during pregnancy. The testing is not comprehensive – individuals with PWS from maternal disomy or imprinting defects will not be identified with this technology.

 

The studies to date are a reminder of why researchers examine new technologies multiple times – the results can vary significantly. These prenatal tests are SCREENING tests only – not intended to make a diagnosis, but to lead the health care team to additional testing if indicated. We are grateful that research continues on behalf of our children and families to help us learn more about testing and causes of PWS.

Psychiatric problems such as depression, anxiety, and psychosis do occur in the teen and early adult years at higher rates than the typical population. Psychotropic medications have greatly enhanced the lives of many people with Prader-Willi syndrome, but not all respond to the same drugs and the same dose. These medications are also not the panacea for all of the complex behavioral and psychiatric issues of the syndrome. Is imperative to have a good understanding of when to use psychotropic medications in conjunction with good management, and what are the unique characteristics of the syndrome that may affect the person’s response to the medication.

Parents may notice subtle changes in behavior prior to a psychiatric crisis; taking action by seeing a mental health professional at this early stage can help avert a decline in mental health.

Psychotropic med tip sheet

The Mental Health of People with Prader-Willi Syndrome with Specific Focus on Mood Disorders and Psychotic Illness

Psychiatric information for psychiatrists

Mental Health and Behavior

 

Both males and females with PWS are likely to have sex hormone and gonadal insufficiencies (ovary and testes).  Since precise pituitary/hypothalamic function is needed to stimulate the gonads, the typical person with PWS will have low sex hormone levels (testosterone and estrogen).

Most girls will have normal early puberty with breast growth, but not have strong enough hormone pulses to start menstrual periods. There is no known abnormality of the ovary in PWS. For boys, the pituitary/hypothalamus weakness creates two separate problems. Before birth, these hormones develop the penis and cause the testicles to move from inside the body to the scrotum. Without good pituitary hormone function, many boys are born with undescended testes, and a smaller penis. Testicles must be located in the scrotum to avoid and detect cancer development; surgery is commonly needed.  Medication can be given early in life to improve penis size, but this does not affect the testicles, which often are not well developed. In addition, most boys have the same puberty problem seen in girls with PWS. The hypothalamus/pituitary gland do not make adequate stimulation hormones for the testes, and puberty may not progress at a normal speed. Hormone replacement (testosterone or estrogen) may be needed for optimal health, such as bone health, muscle strength, and well-being, as well as for full pubertal development.

Fertility is very impaired in persons with PWS. There have been no reports of fertility in men, and only a few cases of pregnancy in women with PWS. Men and women with PWS do not lack in affection or the ability to fall in love; many adults find happiness in having a romantic partner and with hormone replacement, could have full sexual function.

See Adrenarche for another hormone finding which is not the result of the previously described abnormalities.

Puberty

 

S – V

Children with Prader Willi Syndrome have an incidence of developing scoliosis at rates between 40 -90%. There are two peak ages for scoliosis presentation in children with PWS. Under the age of 4 years, the curves are most likely related to the hypotonia (low muscle tone); these are less likely to require treatment. The second peak, centered around 10 years of age, typically is the more common S-shaped curve with a greater chance of needing surgery. Spinal xrays are more accurate than a physical exam at detecting the type of curve seen in PWS. All children with PWS need to be evaluated on a regular basis by an orthopedic surgeon.

Scoliosis monitoring

Scoliosis Surgery

This is a common habit in PWS, without a known cause or effective treatment. These lesions may become infected, and often cause scarring. Insect bites are often the starting point; insect repellents and long sleeves and pants when the person with PWS is outdoors will help with prevention. Individuals with PWS also tend to bruise easily. Appearance of such wounds and bruises may wrongly lead to suspicion of physical abuse.

Publication by Drs. Linda Gourash and Janice Forster of the Pittsburgh Partnership on Skin Picking

Rectal picking poster

Picking and N-acetylcysteine

AllegationsofAbuse

Skin Picking

Sleep problems occur frequently among individuals with PWS. Sleep studies are recommended as standard care for persons with PWS; these are not standard sleep tests, as they need to include testing for central apnea and end tidal CO2, not just obstructive sleep apnea.

The most common problem is excessive daytime sleepiness (EDS). This can be related to sleep apnea but is also commonly seen in individuals with normal sleep studies.

Sleep apnea refers to abnormal breathing while asleep. The most common type is obstructive sleep apnea. Poor muscle tone, large tonsils, or obesity can place pressure on the airway during sleep, when muscles relax naturally. There is not always snoring or restlessness.

Central sleep apnea is not related to weight or obesity. The hypothalamus regulates breathing, and since this part of the brain is generally poorly functioning, that is the most likely explanation for this. It is most common in infants with PWS and can improve over time.

 

Supplements are popular therapies in PWS. Some families report responses such as increased strength in infancy, while others do not see changes with these products. Be aware of herb/drug interactions. Herbs and drugs that have similar purposes (such as sedatives, blood thinners, or stimulants) should not be taken together, nor should herbs and drugs with opposite actions (a sedative herb taken with a stimulant drug, for instance). Ask your local pharmacist about any known adverse reactions.

Communicate with your physician. It is important to tell your doctor of any herbs you are taking, especially before surgery. Blood-thinning, sedative, and stimulant herbs may have adverse effects on surgery and subsequent recovery. Some herbs may interfere with prescribed medications, as well. Be sure to disclose any herbs or supplements you are currently taking if a new medication is prescribed.

Persons with Prader-Willi Syndrome may be more sensitive to medications. Hence, smaller dosages of herbs and drugs may cause the same reaction as larger dosages in other people. Start Low, Go Slow is recommended.

Supplementation Vitamins in high doses

Supplementation CoQ10

 

 

Poor muscles tone, thick saliva, and often uncoordinated swallowing muscles contribute to problems with swallowing. All family members and providers should be able to perform the Heimlich maneuver. No person with PWS should eat alone; even water can be difficult to swallow.

Deaths Due to Choking in Prader-Willi Syndrome

Swallowing Problems in PWS

Swallowing and Silent Aspiration in Infants

Subclinical Dysphagia

Normal range of body temperature can vary significantly in people with PWS. It is important to know the usual “healthy” temperature and monitoring this under different circumstances from time to time to establish a pattern. Lacking good temperature control can mean that a fever will be even higher than in other people.  Keeping comfortable may require different layers of clothing for the person with PWS.

See Hypothermia

Vomiting occurs less frequently in those with PWS, for unknown reasons.  The presence of prolonged or projectile vomiting may signal a life-threatening illness such as a bowel obstruction or gastric rupture and requires medical treatment.  According to the Global PWS registry, 50% of respondants reported that their child has vomitted in the past.

W – Z

Water intoxication has occurred in relation to use of certain medications with antidiuretic effects, as well as from excess fluid intake alone.