Prader-Willi Syndrome

Description

Other Names

Prader-Labhart-Willi syndrome

Diagnosis Coding

ICD-9

759.81, Prader-Willi syndrome

ICD-10

Q87.1, Congenital malformation syndromes predominantly associated with short stature.

ICD-10 Congenital Malformation Syndromes Short Stature Coding Reference provides more detail.

Description

Prader-Willi syndrome (PWS) is the most common genetically identified cause of life-threatening obesity in humans. Diagnosis and management of PWS requires a multidisciplinary approach and early diagnosis to achieve the best health outcomes. The primary features of PWS include:

  • A characteristic appearance with small upturned nose, narrow bifrontal diameter, dolichocephaly, down-turned corners of the mouth, distinctive eyes (described as almond-shaped), and strabismus
  • Infantile hypotonia that improves with age, though most remain relatively hypotonic
  • Feeding difficulties and failure to thrive in the early years
  • Hyperphagia and subsequent early onset of childhood obesity
  • Developmental delay/intellectual disability
  • Hypogonadism
  • Behavior problems (temper tantrums, stubbornness, obsessive-compulsive behaviors, skin picking)
  • Small hands and feet
  • Endocrine disturbances, including growth hormone deficiency
  • Sticky saliva
Those with PWS and the 15q11-q13 deletion may also have hypopigmentation relative to family background.

Prevalence

The prevalence of PWS is approximately 1/25,000. [Butler: 1990] It affects an estimated 350,000 to 400,000 people worldwide, including 17,000 to 22,000 individuals in the United States. It is present in all races and ethnic groups, but reported disproportionately in Caucasians. [Butler: 2006] The Diagnosis Prevalence List can be used by medical practices to predict statistically the number of children who might be seen with Prader-Willi or other complex medical conditions.

Genetics

Most cases of PWS are sporadic; however, at least 20 families have been reported with more than one affected member, including reports in twins. The chance for familial recurrence is estimated to be less than 1%. However, this risk may be as high as 50% in some families where an imprinting defect causes defective control of differentially expressed genes in both the PWS child and the unaffected father.

PWS is a complex genetic syndrome resulting from the absence of expression of genes found in the region of the paternally inherited 15q11-q13 chromosome region, most commonly due to a paternal 15q11-q13 deletion. There are three recognized genetic subtypes:
  1. A paternal de novo deletion of 15q11-q13 (70% of cases)
  2. Maternal disomy 15, where both chromosomes 15 come from the mother (25-29% of cases)
  3. An imprinting defect (in the remaining subjects) with a microdeletion of the imprinting center or an epimutation controlling the expression of imprinted genes in the region. (Imprinting is the process by which maternally and paternally derived chromosomes are uniquely chemically modified leading to different expression of a certain gene or genes on those chromosomes depending on their parental origin. An epimutation is a heritable change in the gene expression, such as through DNA methylation, which occurs without changing the base pair sequence of the DNA.)
The Medical Home Portal's Prader-Willi Syndrome Genetics page and Prader-Willi Syndrome Review (GeneReviews) provide more detailed genetic information.

Prognosis

If obesity is avoided and complications are well managed, life expectancy for individuals with PWS is normal or near normal and most individuals can lead healthy lives. [Butler: 2006] Early education of caregivers and maintenance of a controlled environment are essential to a good outcome.

Roles Of The Medical Home

The medical home should collaborate with specialized multidisciplinary services when available (Multi-Disciplinary Management for Prader-Willi Syndrome), assure that primary care complements specialty services, and coordinate school and other community-based services. When no multi-disciplinary clinic is available, the medical home may take on the role of helping the family with coordinating care, and accessing specialists and appropriate community-based services. Managing the care, and particularly the nutrition and behavior, of children with PWS is very challenging - collaborating with and providing support for the family is a key role of the medical home provider.

Practice Guidelines

McCandless SE.
Clinical report—health supervision for children with Prader-Willi syndrome.
Pediatrics. 2011;127(1):195-204. PubMed abstract / Full Text

Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M.
Recommendations for the diagnosis and management of Prader-Willi syndrome.
J Clin Endocrinol Metab. 2008;93(11):4183-97. PubMed abstract / Full Text

Helpful Articles

PubMed search on Prader-Willi syndrome: articles over the last 10 years

Butler MG, Lee PDK, Whitman, BY.
Management of Prader-Willi Syndrome.
3rd ed. New York, NY: Springer Verlag Inc.; 2006. 0387253971
Textbook with diagnosis and management information for PWS. Includes clinical, genetic, social, family, and community issues.

Butler MG, Roberts J, Hayes J, Tan X, Manzardo AM.
Growth hormone receptor (GHR) gene polymorphism and Prader-Willi syndrome.
Am J Med Genet A. 2013;161A(7):1647-53. PubMed abstract / Full Text

Butler MG.
Prader-Willi syndrome: obesity due to genomic imprinting.
Curr Genomics. 2011;12(3):204-15. PubMed abstract / Full Text

Cassidy SB, Schwartz S, Miller JL, Driscoll DJ.
Prader-Willi syndrome.
Genet Med. 2012;14(1):10-26. PubMed abstract / Full Text

Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS.
GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome.
J Clin Endocrinol Metab. 2013;98(6):E1072-87. PubMed abstract / Full Text

Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold JA, Kimonis V, Dykens E, Butler MG, Shuster JJ, Driscoll DJ.
Nutritional phases in Prader-Willi syndrome.
Am J Med Genet A. 2011;155A(5):1040-9. PubMed abstract / Full Text

Clinical Assessment

Overview

A diagnosis of PWS is usually suspected because of clinical findings and is confirmed through genetic testing. The timing of the diagnosis may depend on the severity of the symptoms or access to health care professionals familiar with the diagnosis and it will have an impact on clinical management. Please see Multi-Disciplinary Management for Prader-Willi Syndrome for details on necessary evaluations for children with this disorder.

Screening

For The Condition

Although no newborn screening is underway at the state level, infants presenting with severe hypotonia, a poor suck, and feeding difficulties without a clear underlying cause should have DNA methylation testing and microarray analysis to diagnose PWS, if present, and the genetic subtype.

Of Family Members

Depending on the PWS genetic subtype identified by microarray analysis, screening parental DNA may be required for further characterization (deletion, maternal disomy, or imprinting defect). The genetic subtype may impact medical management and genetic counseling with recurrence risk estimates (< 1% for the typical 15q11-q13 deletion or as high as 50% if a micro-deletion is the cause of an imprinting defect).

For Complications

Depending on the obesity status, co-morbidities may exist including diabetes mellitus, hypertension, inflammation, a fatty liver, and orthopedic problems. Therefore, laboratory evaluations (liver function, insulin, glucose, and lipid levels) should be monitored along with thyroid function and inflammatory markers during regular health examinations.

Presentations

The diagnosis or suspected diagnosis is based on clinical findings and confirmed by genetic testing. Clinical findings will vary with age as the course of PWS has historically been divided into two clinical stages. The first stage presents with profound hypotonia, feeding difficulties and poor weight gain, and developmental delays. The second stage, which begins sometime between ages 2 and 4, is characterized by the onset of hyperphagia leading to obesity and continued developmental delays. Based on nutritional phases, caloric intake and weight, four clinical phases have recently been described in PWS, as discussed below under Diagnostic Criteria.

Diagnostic Criteria

A consensus diagnostic criteria for PWS was initially developed [Holm: 1993]; revised diagnostic criteria came out in 2001. [Gunay-Aygun: 2001] The clinical criteria are based on the individual's age and clinical presentation and are used to prompt genetic testing (see Genetic Testing, below) to confirm the clinical findings:
  • Birth to 2 years:
    • Recognizable facial features, hypotonia with related feeding difficulties and failure to thrive, hypogonadism.
  • 2 to 6 years:
    • Recognizable facial features, hypotonia with gross motor delays, development of hyperphagia and weight gain, typically shorter stature and smaller OFC.
  • 6 to 12 years:
    • Development of unusual behaviors, learning disabilities, and cognitive impairments.
    • Physical features may be more difficult to recognize, hands and feet may become relatively smaller in these years.
    • Excessive eating with central obesity if uncontrolled.
  • 13 years to adulthood:
    • Cognitive impairment, usually mild intellectual disability;
    • Excessive eating with central obesity if uncontrolled; and
    • Hypothalamic hypogonadism and or typical behavior problems.

Clinical Classification

Advances in genetic technology allow for more accurate and early identification of PWS and genetic subtypes. Primarily, those with the larger type I deletion have more behavioral problems; similarly, more clinical variation is seen in those with maternal disomy 15, or in those rare PWS individuals with imprinting defects (microdeletions or epimutations).

Differential Diagnosis

The differential diagnosis of PWS varies depending on the age of the patient. During infancy and the failure to thrive stage, the differential diagnosis includes:
  • Neonatal sepsis
  • Central nervous system anomalies
  • Inborn errors of metabolism
  • Microdeletions of 1p36.3, 6q16.2 or 16q12.2 may involve obesity-related genes such as FTO, MC4R or SIM1 and several features similarly seen in PWS
  • Infantile botulism
  • Myotonic Muscular Dystrophy Type 1 (Portal module with diagnosis and management information)
  • Spinal Muscular Atrophy (Portal module with diagnosis and management information)
During childhood and the hyperphagic obesity stage of PWS, the differential diagnosis includes:
  • Familial obesity
  • Fragile X Syndrome (Portal module with diagnosis and management information)
  • Inborn errors of metabolism
  • Leptin deficiency (very rare)
  • SIM 1 gene mutations and 16p deletion
  • Albright hereditary osteodystrophy
  • Bardet-Biedl, Alstrom, and Cohen syndromes
  • Chromosomal abnormalities including 1p36 deletion, 3p25 duplication, and uniparental disomy 14
See Online Mendelian Inheritance in Man (OMIM) for more information on specific syndromes.

Comorbid Conditions

Comorbid conditions are recognized in PWS such as obesity, diabetes, scoliosis, gastric motility, and self-injury. These are addressed elsewhere in the module.

Pearls & Alerts

Ear and other infections with minimal pain

Because children with PWS have decreased pain sensation, the child may not display the discomfort usually associated with otitis media, strep throat, or other infection. Any child with fever over 101 degrees should be evaluated by their medical home provider.

Osteoporosis in children with PWS

Due to poor calcium intake secondary to strict dietary control, decreased exercise, and hormone therapy, children with PWS may develop osteoporosis. Osteoporosis in Children with Prader-Willi Syndrome provides further information.

History & Examination

Family History

Not likely to be helpful because the majority of cases are sporadic.

Pregnancy Or Perinatal History

Ask about fetal movement, which is often limited and of low velocity, and consistent with hypotonia. Depressed Apgar scores at birth may occur due to hypotonia. Infants with PWS are typically born at or near term and often have a slightly low, but not unusually abnormal birth weight. Ask about perinatal problems, particularly a history of poor feeding and low tone.

Current & Past Medical History

Ask about:
  • Hyperphagia, rumination, and episodes of gastric distention
  • Problems with feeding and failure to thrive in infants
  • Hyperphagia in older children and what management is being used, e.g., diet, exercise, or behavior modification
  • The use of growth hormone therapy and testosterone or estrogen replacement therapy
  • Symptoms of diabetes including frequent urination, acanthosis nigricans, etc.
  • Energy level, constipation, and growth with consideration of hypothyroidism
  • Self-injurious behavior including nose and skin picking or other obsessive behaviors
  • Chronic respiratory infections, reactive airway disease
  • Problems while sleeping, including snoring, daytime sleepiness, and frequent arousals. Individuals may have sleep apnea, obstructive, central, or mixed, and hypoventilation with hypoxia. The Medical Home Portal's Sleep Problems (general) issue page provides further information on sleep disorders.

Developmental & Educational Progress

Ask about:
  • Learning problems and symptoms of hyperactivity
  • Speech articulation problems - consider referral to a speech-language therapist for further evaluation.
  • Achievement of developmental milestones and, later, educational progress
  • Behavior problems and obsessive-compulsive features
Attention Deficit Hyperactivity Disorder (ADHD) is common in individuals with PWS (up to 22%) and symptoms should be sought during the history. [Wigren: 2005] In older children and adults with PWS, ask about signs of psychosis such as auditory hallucinations and disordered thinking.

Maturational Progress

In older children and adolescents with PWS, ask about pubertal progress.

Social & Family Functioning

Ask about the child's social abilities and interactions with other children, and about family functioning, including the availability of resources and supports from community groups and extended family.

Physical Exam

General

Hypotonia, a poor suck, and feeding problems are common in infants in PWS. Look for characteristic appearance including dolichocephaly, narrow bifrontal diameter, distinctive (almond-shaped) eyes, small up-turned nose, and down-turned corners of the mouth. [Holm: 1993] [Butler: 1990] [Cassidy: 2012] Small hands and feet are also present in the majority of individuals with PWS. Assess alertness, activity level, and interactions for age-appropriateness.

Vital Signs

HR | BP | RR, breathing difficulties

Growth Parameters

Weight, height, and BMI. Short stature is present in the majority of individuals with PWS. Regular evaluation of growth is important when children receive growth hormone, including OFC. [McCandless: 2011] Growth charts can be found at:
Food seeking (hyperphagia) and decreased energy expenditure leads to obesity in early childhood (if uncontrolled). Regular health care examinations and surveillance are required to monitor for health issues related to obesity and its complications.

Skin

Look for areas of excoriation due to skin picking. Check for acanthosis nigricans.

HEENT

  • Screen regularly for eye problems, such as strabismus, myopia, and other problems with visual acuity, at least every 1 to 2 years.
  • Screen for eye problems, such as strabismus and visual acuity, which should be done at 1 year of age and as needed every 1 to 2 years.
  • Monitor size of tonsils and adenoids, particularly in obese individuals.
  • Check ears and throat for infection.
  • Check nares for sores from nose picking.

Mouth/Teeth

  • Look for sticky saliva. Decreased saliva flow and sticky salivary secretions can impact dental care and hygiene.
  • Look for dental enamel defects. Enamel hypoplasia is common and can lead to cavities, which is further complicated by rumination seen in a subset of individuals with PWS.

Chest

Respiratory distress with shallow breathing and central sleep apnea problems may compromise oxygen saturation, pulmonary function, and breathing.

Heart

Listen for murmurs and gallops that may be a sign of hypertrophy or right-sided heart failure; look for hepatomegaly or peripheral or sacral edema.

Abdomen

Distended abdomen and decreased audible bowel sounds may be present in PWS and be related to increased central adiposity. Constipation and decreased gastric motility and risk for increased colon size are common, requiring close observation. People with PWS also have a high pain threshold, which can impact the reliability of the abdominal exam.

Genitalia

  • Check for cryptorchidism and check Tanner stage and appearance of genitals.
  • Check for signs of rectal ulcers due to skin picking.
  • Look for signs of monilial or bacterial infection in deep skin folds.

Extremities/Musculoskeletal

  • Check spine for scoliosis and kyphosis and monitor closely particularly if on growth hormone therapy.
  • Check for dysplastic hips.
  • Look for edema and skin changes in the legs in obese individuals. Fluid retention is usually noted first as swelling of the lower legs. Fluid retention in persons with PWS is usually a sign of a decreased ability to breathe adequately due to excessive weight.

Neurologic Exam

Look for hypotonia in infants and toddlers. Relative hypotonia may be present in older children.

Testing

Sensory Testing

No specific sensory problems associated with PWS; however, regular visual and hearing screening are recommended.

Laboratory Testing

Growth hormone deficiency is common in PWS. IGF-1 should be monitored regularly during growth hormone treatment. [Deal: 2013] Provoked GH response can be tested as well, particularly in adults.

Thyroid hormone levels should be checked and monitored routinely if replacement therapy is needed. [Deal: 2013]

Laboratory evaluation of liver function, insulin, glucose, lipid levels, and inflammatory markers should be monitored routinely, with frequency based on obesity and presence of comorbid conditions. [Deal: 2013]

Consider performing ACTH stimulation testing to rule out central adrenal insufficiency, which has been recently reported to occur in PWS. [de: 2008]

Imaging

Consider AP and lateral spine films to evaluate for scoliosis. Spinal deformities are estimated to occur in 40-90% of children with PWS. The Prader-Willi Syndrome Association (USA) recommends yearly screening as deformities may not be clinically visible.

Bone age testing is part of the assessment prior to starting growth hormone. [Deal: 2013]

DEXA Scan: Because children with PWS may have multiple risk factors for osteoporosis, consider a DEXA scan to evaluate for body composition including bone density for osteoporosis, particularly in the setting of a fracture or fractures.

Genetic Testing

Genetic testing is complex and recommended approaches to genetic testing for children suspected of having PWS vary among specialists - consulting pediatric genetics in your area is advised. If the diagnosis is confirmed, identification of the genetic subtype is important to guide clinical management and to advise regarding recurrence risks. See Flowchart of Recommended Molecular Testing Strategy for PWS (AAP) from [McCandless: 2011] for more information.

CNV/SNP microarray analyses: Recent report of GHR gene polymorphism may impact growth rate acceleration. Testing for this polymorphism, which is seen in about 50% of Caucasian individuals and may contribute to the rate of scoliosis, should be considered in the treatment and care of PWS infants, children, and adolescents while undertaking GH treatment. [Butler: 2013]

See Prader-Willi Syndrome Genetics for more information, PWS Genetic Testing (GeneTests) for laboratories that offer testing for PWS, and Subspecialist Evaluations, below, for consultation resources.

Other Testing

Consider a sleep evaluation if the child has snoring, frequent awakenings, excessive daytime sleepiness, or other sleep problems. A sleep study is considered mandatory prior to initiation of growth hormone therapy. [Deal: 2013]

Consider screening questionnaires for family and school if ADHD is suspected. For more information, see National Resource Center on ADHD, Caring for Children with ADHD Toolkit (AAP), and Attention Deficit Hyperactivity Disorder (ADHD) for diagnosis and management guidance.

Subspecialist Collaborations & Other Resources

Pediatric Genetics (see Services below for relevant providers)

Refer for guidance in the genetic evaluation and diagnosis of children suspected of having PWS, and for genetic counseling for families. Geneticists will also consider other conditions if the diagnosis is not confirmed. The genetic specialists can help the family access support groups and relevant studies.

Pediatric Endocrinology (see Services below for relevant providers)

Refer for expertise in managing growth and other endocrine problems that are common in children with PWS (e.g., hypothyroidism, delayed secondary sexual characteristics).

Developmental Pediatrics (see Services below for relevant providers)

Consultation can be helpful in managing challenging behaviors in children with PWS.

Pediatric Orthopedics (see Services below for relevant providers)

Refer for periodic or PRN assessment of children with PWS for hip dysplasia, scoliosis, and complications of obesity.

Psychologist, Child-18 (see Services below for relevant providers)

Refer for evaluation and management of behavior problems including hyperphagia, tantrums, and obsessive-compulsive behaviors, as well as assessment of IQ and achievement testing to allow educational planning.

Pediatric Ophthalmology (see Services below for relevant providers)

Refer for evaluation and management of strabismus, myopia, and other visual problems.

Pediatric Gastroenterology (see Services below for relevant providers)

Consult for assistance with feeding problems, including failure to thrive, hyperphagia/obesity, rumination, and gastric dilatation.

Pediatric Otolaryngology (see Services below for relevant providers)

If indicated, refer to assess the contribution of enlarged tonsils and adenoids to sleep problems.

Pediatric Dentistry (see Services below for relevant providers)

Refer for evaluation and treatment of enamel defects and decreased saliva.

Pediatric Sleep Medicine (see Services below for relevant providers)

Consult for sleep studies or difficult-to-manage sleep-related behaviors.

Treatment & Management

How should common problems be managed differently in children with Prader-Willi Syndrome?

Growth Or Weight Gain

Obesity should be controlled and body composition (% fat or lean mass) measured with DEXA to monitor and lower risks for developing co-morbidities including diabetes mellitus, type 2 (DM2). Standardized growth charts developed for non-GH treated PWS children (0-3 years) subjects are particularly helpful to gauge and monitor growth and development while on growth hormone therapy, and caloric restriction diets and exercise programs to control weight during the failure to thrive phase during infancy and to later ages where increased weight gain becomes a problem. Non-GH treated PWS growth curves are also available for those between 3 – 18 years. These charts can be found at:
Nutrition and access to food should be carefully managed. Strictly controlling access to food is one of the most basic skills taught to the family or other caretakers. It involves three criteria:
  1. There is no doubt when, what, and how much the person with PWS will eat.
  2. There is no hope of receiving any more.
  3. There is no disappointment due to false expectations.
When food access is restricted, individuals with PWS require no doubt about their meals and snacks. Menus are planned and posted; calories are controlled, but the amount of food presented can still be generous. Although the timing of the meals and snacks remains fixed, it is not focused on the clock; it is set by the sequence of activities across the day. This concept is critical to the achievement of flow through the day. Securing Food = No doubt + No hope + No disappointment. Guidance on nutrition can be obtained by working with a dietician, particularly one familiar with PWS. Healthy diet information can be found at Red-Yellow-Green Weight Control System and Traffic Light Diet Common Food List(PDF Document 140 KB).

Bacterial Infections

Monitor for bacterial and fungal skin infections at sites of skin picking and in skinfold (fat) creases.

Prescription Medications

People with PWS may have unusual reactions to standard dosages of medications. Use extreme caution in giving medications that may cause sedation: prolonged and exaggerated responses have been reported. Carefully monitor respiratory function.

Common Complaints

Vomiting rarely occurs in individuals with PWS, even when it may be helpful. Emetics may be ineffective and repeated doses may cause toxicity. This characteristic is of particular concern in light of hyperphagia and the possible ingestion of uncooked, spoiled, or otherwise unhealthful food.

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

High pain tolerance or lack of typical pain signals is common and may mask the presence of infection or injury. Someone with PWS may not complain of pain until infection is severe or may have difficulty localizing pain. Parent/caregiver reports of subtle changes in condition or behavior should be investigated for medical cause. Discomfort due to high fiber or other gas-stimulating foods should also be considered.

Pearls & Alerts

Central adrenal insufficiency

Individuals with PWS may present with central adrenal insufficiency. The amount of cortisol they produce may not be adequate during times of stress (e.g., illness, trauma, or surgery). See [de: 2008] and [Stevenson: 2004]. ACTH stimulation testing can be used to evaluate for central adrenal insufficiency. [de: 2008]

Water intoxication

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

High pain tolerance

High pain tolerance or lack of typical pain signals is common and may mask the presence of infection or injury. Someone with PWS may not complain of pain until infection is severe or may have difficulty localizing pain. Parent/caregiver reports of subtle changes in condition or behavior should be investigated for medical cause.

Risk of respiratory and sleep problems

Individuals with PWS may be at increased risk of respiratory problems. Hypotonia, weak chest muscles, and sleep apnea are potential complicating factors. Anyone with significant snoring, regardless of age, should have a medical evaluation to look for obstructive sleep apnea. Infants may be at risk for respiratory failure when they are ill due to the increased risk of obstruction. Laboratory evaluation of respiratory function may be necessary.

Risk of complications from anesthesia

Children with PWS have increased risk of complications from anesthesia, including trauma to the airway, oropharynx, or lungs due to physiologic differences (such as narrow airway, underdevelopment of the larynx and trachea, hypotonia, edema, and, scoliosis). Particularly with the increasing number of infants and children with PWS undergoing sleep assessments and a potential rise in surgical procedures for obstructive sleep apnea, it is important to alert the medical team to potential complications. See also Guidelines for Postoperative Monitoring of Pediatric Patients with Prader-Willi Syndrome (PWSA USA).

Temperature dysregulation

Temperature dysregulation, resulting in high or low body temperatures, has been reported in PWS without evidence of infection or other known cause. However, hyperthermia may occur during minor illness and in procedures requiring anesthesia. Fever may be absent despite serious infection.

Skin lesions

Skin lesions in individuals with PWS, including open sores caused by skin picking, and easy bruising, may wrongly lead to suspicion of physical abuse. Skin picking is usually in response to an existing lesion or from itching of the face, arms, legs, or rectum. It is best managed by ignoring the behavior, treating and bandaging sores, and providing substitute activities for the hands. Close observation for prolonged bathroom time and other activities should be monitored to avoid self-injurious behavior.

Hyperphagia

Hyperphagia due to insatiable appetite may lead to life-threatening weight gain, or may lead to stomach necrosis and rupture. Weight gain may be very rapid and occur even on a low-calorie diet. Individuals with PWS must be supervised at all times in all settings where food is accessible.

Growth hormone deficiency

All individuals with PWS should be considered growth hormone deficient. The FDA has recognized a diagnosis of PWS as an indication for growth hormone therapy. Although currently in the investigational stage, in the future genetic testing for GH receptor gene polymorphism may help guide use of GH treatment in adulthood to improve quality of life in PWS [Butler: 2013] [Butler: 2013]

In the event of death

In the event of death of an individual with PWS, please contact the Prader-Willi Syndrome Association (USA), which maintains a research database of reported deaths. Although most premature deaths are attributable to morbid obesity, cases unrelated to obesity have recently been noted, leading PWSA to recommend a formal investigation of causes of death. PWSA also provides bereavement support to families who have lost children with PWS.

The family may also wish to consider donation of organs for research. PWSA (USA) has established a procedure for Tissue Donation (PWS Association) to support research on PWS, created by the NIH in cooperation with the University of Maryland and the University of Miami. Prompt action is essential for tissue preservation. Families are advised to contact the closest Brain and Tissue Bank (800-847-1539, Maryland) directly.

Systems

Endocrine/Metabolism

Growth hormone is typically deficient in PWS, causing short stature, lack of a pubertal growth spurt, and a high body fat ratio (fat/body weight), even in those with normal weight. Growth hormone (GH) is approved for use in PWS for improvement of body composition, height velocity and linear growth, mobility, behavior, and quality of life. Growth hormone therapy may increase muscle mass and function and allow a higher daily calorie intake. Psychosocial development may also be improved. Therapy is initiated at a standard dose of approximately 0.5 mg/kg/wk divided as a daily subcutaneous injection. [Deal: 2013] See the Growth Hormone Policy Statement (PWSA) and the updated international guidelines for growth hormones at [Deal: 2013] for more information.

Due to reports of sudden death during initiation of GH, mainly during sleep and possibly related to severe obesity and sleep disordered breathing, families must be counseled prior to starting GH therapy. [Deal: 2013] Baseline and follow up studies and labs include sleep study, IGF-1, thyroid, metabolic and liver function, lipids, DEXA scan, and possibly adrenal function with AM cortisol level. [Deal: 2013]

Diabetes mellitus, type II, has been observed in individuals with PWS, particularly in those individuals with obesity. The risk for diabetes is lowered when weight is reduced. Therefore, blood glucose (fasting glucose, HgbA1c) and fasting insulin levels are periodically checked depending upon the level of obesity and use of growth hormone therapy. Oral glucose tolerance test can be considered. [Deal: 2013]

Sex hormones and sexual maturation is addressed below in the Maturation/Sexual/Reproductive sexual of the module.

Subspecialist Collaborations & Other Resources

Pediatric Endocrinology (see Services below for relevant providers)

Referral and co-management for growth hormone initiation and treatment, monitoring for diabetes mellitus, and possibly for sex hormone replacement.

Pediatric Genetics (see Services below for relevant providers)

Periodic referrals are recommended for collaboration on ongoing management.

Prader-Willi Clinics (see Services below for relevant providers)

If available, management at a PWS Clinic is recommended.

Gastro-Intestinal & Bowel Function

Failure to thrive: Food intake during the first two years of life requires close management to maintain weight-for-height measures between the 25th and 80th percentile. Failure to thrive may necessitate tube feeding. Infants with PWS should be closely monitored for adequate calorie intake and appropriate weight gain. Referral to pediatric gastroenterology may be indicated. Published growth standards specifically for use in PWS are available at: Hyperphagia: In older children, hyperphagia due to insatiable appetite may lead to life-threatening weight gain, which can be very rapid and occur even on a low-calorie diet. Excessive uncontrolled over-eating may lead to stomach necrosis and rupture. To control energy intake, a careful food-monitoring program is essential for both children and adults with PWS. [Butler: 1991] Restricted caloric intake with vitamin and calcium supplementation, performed under the close supervision of an experienced dietitian, is generally required from age 2-3 years to minimize excessive weight gain and osteoporosis. Successful weight maintenance in children with PWS who have not been treated with growth hormone has been reported with an intake of 8-11 kcal per cm of height per day, whereas children without PWS require 11-14 kcal per cm per day for adequate growth.

Individuals with PWS must be supervised at all times in all settings where food is accessible. Those who have normal weight have only achieved this because of strict external control of their diet and food intake. Involving the patient, family members, and care providers is critical in developing strategies to cope with the hyperphagia, weight, and behavior control issues that are characteristic of PWS. [Goldberg: 2002] Tactics include:
  • locking away food,
  • keeping limited amounts of food in the home,
  • continual close supervision of the patient around food or food-related events,
  • providing non-food-related rewards,
  • reduction of portion sizes using small plates and bowls,
  • allowing participation in menu planning and preparation,
  • counting calories, and
  • having access to food with fewer calories.
It is also important to keep strict mealtime regimens and to ensure unwavering consistency by both parents and care providers, both inside and outside of the home. See Food and Behavior in PWS (Pittsburgh Partnership) for more information. Individually tailored exercise programs are encouraged - 30 minutes of sustained activity 3-5 times per week are generally recommended. [Butler: 2006] [Holm: 1976] To date, no medication or surgical intervention has been found that would eliminate the need for strict dieting and supervision around food. Bariatric surgery has generally been unsuccessful and not recommended in PWS. [Scheimann: 2008] See also Obesity and Complications in Prader-Willi Syndrome.

Gastroesophageal reflux (GER) is common in children with PWS and may be particularly problematic in infants due to their hypotonia. The Medical Home Portal’s page on Gastroesophageal Reflux (general) provides further information.

Vomiting and rumination: Commonly reported features of PWS include a decreased ability to vomit and a high prevalence of rumination. [Alexander: 1987] Dental enamel defects due to rumination should be looked for routinely. Rumination may increase in children with strict behavioral food intake programs. See Rumination (eMedicine) for more information.

Constipation is common in children with PWS (>20%). Rectal ulcers, which may occur due to skin picking, can be exacerbated by large stools and constipation. Treatment of bowel disorders in individuals with PWS often requires ongoing specialized treatment and monitoring with a multi-disciplinary approach to optimize therapy. The You Can Poop Too Program (BeHealth Solutions) is an online program that helps solve the physical, emotional, and behavioral issues of encopresis. The Medical Home Portal’s page on Constipation Treatment (general) has information about the evaluation and treatment of constipation. The following tools may be helpful: Bowel Management Algorithm(PDF Document 47 KB); Bowel Management Parent Information; Bowel Management (general)(PDF Document 74 KB); Constipation Evaluation Tool(PDF Document 84 KB); and, Home Toileting Record(PDF Document 49 KB).

Fatty liver (hepatic steatosis): Monitor ALT and AST and consider liver ultrasound or biopsy in obese individuals. [Deal: 2013]

Decreased sensitivity to gastric fullness and pain: Although they have no known congenital defects involving the gastrointestinal system, children with PWS have decreased sensitivity to gastric fullness and to pain. A decreased pain response may mask the symptoms of gastrointestinal problems such as gastric distention, gastroparesis, and necrosis, which are common in individuals with PWS. In addition, because vomiting is reduced in children with PWS, they may not respond to eating spoiled or contaminated foods. Children with PWS may present with behavior changes and vague feelings of unwellness that might represent medically urgent gastrointestinal disease. These complaints should be taken seriously by providers.

Subspecialist Collaborations & Other Resources

Pediatric Gastroenterology (see Services below for relevant providers)

A referral to gastroenterology may be helpful for management of failure to thrive, and hyperphagia, severe reflux, constipation, or fatty liver.

Nutrition/Dietary (see Services below for relevant providers)

It is important to involve nutrition expertise on a regular basis for both failure to thrive and the restricted diet necessary for children and adolescents with PWS.

Pediatric Genetics (see Services below for relevant providers)

Periodic visits with genetics are helpful for management of growth issues specific to PWS.

Prader-Willi Clinics (see Services below for relevant providers)

When available, management at a PWS Clinic is preferred.

Mobility/Function/ADLs/Adaptive

A number of nutritional issues arise in children with PWS. These include problems with poor feeding and failure to thrive in early infancy, often requiring the use of special nipples or tube feedings. These generally start to improve by 6 months of age, however insatiable appetite and the resulting risks may begin by 12 months of age. Some of these risks are addressed under Gastro-Intestinal above. For more detail, please see the Nutrition and Diet in Prader-Willi Syndrome issue page.

Subspecialist Collaborations & Other Resources

Nutrition/Dietary (see Services below for relevant providers)

It is essential to involve nutritionists familiar with this disorder in diet planning.

Skin & Appearance

A common problem that may become a habit in children with PWS is scratching and picking at the skin or mucosal areas of the face, arms, legs, or rectum. The problem is sometimes triggered by insect bites or other skin lesions. Skin picking behavior may vary in severity and duration; anxiety, stress, or boredom seems to increase the severity of the picking behavior. Over half of adolescents and adults with PWS exhibit this self-injurious behavior. Frequent nose bleeds or rectal bleeds should prompt further examination for sores from picking. Rectal ulcers may occur as a result of rectal itching or “digging.”

Treatment includes keeping the fingernails short, behavior modification, limiting the time spent in the bathroom to reduce opportunities for rectal picking, and providing substitute activities for the hands. Skin and mucosal infections can be managed with topical antibiotics, bandaging, and, if necessary, oral antibiotics. Oral topiramate has been shown to reduce skin picking in some cases. [Shapira: 2002]

The very obese individual is also more prone to fungal and bacterial infections, severe ulceration, and cellulitis due to the inability to cleanse the skin in deep fat folds. Management includes daily cleansing in these folds and air drying with a heat lamp or hair dryer, and the use of medications for infections.

Subspecialist Collaborations & Other Resources

Pediatric Dermatology (see Services below for relevant providers)

May be helpful for those with more severe skin problems.

Pediatric Gastroenterology (see Services below for relevant providers)

If rectal picking continues, gastroenterology may be helpful to treat underlying conditions, such as constipation.

Cardiology

Cardiovascular risk is higher in individuals with PWS for a variety of reasons, including:
  • overeating and obesity,
  • poor dietary habits,
  • diabetes,
  • excess work of breathing, and
  • unexplained elevations of C-reactive protein in individuals with PWS.
These factors may result in hypertension, left ventricular hypertrophy, and right-sided heart failure, particularly in morbidly obese individuals. Although these are not generally present in young children with PWS, older individuals should be referred to a cardiologist for management as needed. Relevant studies include fasting lipid panel (total cholesterol, triglycerides, LDL, and HDL)

Subspecialist Collaborations & Other Resources

Pediatric Cardiology (see Services below for relevant providers)

Helpful in evaluating and managing cardiac risks.

Sleep

Apnea: Up to 90% of children and adults with PWS will have apnea and profound hypoventilation during sleep. [Butler: 2006] This may be due to extrinsic factors such as large tonsils and/or an intrinsic sleep disorder, probably related to hypothalamic dysfunction. Symptoms associated with the sleep disorder may include:
  • hypoventilation,
  • oxygen desaturation during REM sleep,
  • sleep apnea,
  • nocturnal enuresis, and
  • excessive daytime sleepiness and snoring.
If sleep evaluation finds apnea, consider referral to otolaryngology for evaluation of tonsils and adenoids and/or to a pulmonologist or sleep specialist to consider options such as BIPAP or CPAP. A sleep study is performed before starting GH treatment, with a follow-up study 3-6 months later. [Deal: 2013] Surgical management of the obstructive airway should be performed prior to starting GH. [Deal: 2013] Interestingly, in most individuals with sleep-disordered breathing due to PWS, GH can actually improve (or at least not worsen) the apnea. [Haqq: 2003] [Miller: 2006] [Festen: 2006]

Nocturnal enuresis may occur secondary to other underlying sleep problems or as an independent problem. If medical treatment is being considered, for example with DDAVP, start with smaller doses than those used in the general population and gradually increase the dose as needed.

Subspecialist Collaborations & Other Resources

Pediatric Pulmonology (see Services below for relevant providers)

For help in evaluating and managing persistent sleep problems.

Pediatric Otolaryngology (see Services below for relevant providers)

For evaluation and surgery for large adenoids or tonsils in those with obstructive sleep apnea.

Sleep Studies/Polysomnography (see Services below for relevant providers)

For help in evaluating and managing persistent sleep problems

Respiratory

Individuals with PWS may be at increased risk for respiratory problems, especially as infants. Problems at birth, due to hypotonia, weak chest muscles, and poor swallowing reflexes, may include asphyxia, apnea, respiratory failure, and hypoventilation.

Subspecialist Collaborations & Other Resources

Pediatric Pulmonology (see Services below for relevant providers)

For evaluation and management of difficult respiratory problems.

Musculoskeletal

Individuals with PWS commonly have decreased muscle mass and strength. The few histologic and ultrastructural studies of muscle fibers performed in individuals with PWS have found only minimal abnormalities. A disuse or minimal myopathy may accompany central hypotonia in individuals with PWS. [Sone: 1994] Physical therapy and regular participation in exercise programs are essential to improve muscle strength and decrease fat mass. See the Motor Development in Children with Prader-Willi Syndrome issue page. Growth hormone therapy and testosterone therapy in adolescent and adult males also improve muscle strength in individuals with PWS.

Individuals with PWS may also present with scoliosis, kyphosis, and/or lordosis. Progression may occur with the increased linear growth during late childhood and adolescence. Treatment with growth hormone or anabolic steroids may exacerbate scoliosis. Scoliosis may compromise lung function and cause discomfort. Children with PWS should be screened regularly for scoliosis and, if scoliosis is present, referred to a pediatric orthopedic surgeon for management. Surgery to correct the scoliosis is sometimes necessary.

Hip dysplasia is observed in approximately 13% of individuals with PWS and should be screened for by the medical home provider with referral to an orthopedic surgeon if suspected. Hip ultrasound studies during infancy should be considered.

Osteoporosis is found in up to 50% of adolescents and adults with PWS. [Kroonen: 2006] and should be considered in individuals with any fracture that is not consistent with the force of injury. If present, calcium and vitamin D intake should be maximized and the provider should consider a referral to endocrinology. For more information, please see Osteoporosis in Children with Prader-Willi Syndrome and Calcium and Vitamin D (general).

Subspecialist Collaborations & Other Resources

Pediatric Orthopedics (see Services below for relevant providers)

Regular visits starting soon after diagnosis are helpful for screening and management of hip dysplasia, scoliosis/kyphosis, and orthopedic complications of obesity.

Physical Therapy (see Services below for relevant providers)

Regular visits are recommended to supervise conditioning and manage exercise in children with PWS.

Pediatric Endocrinology (see Services below for relevant providers)

Guides evaluation and treatment of osteoporosis.

Prader-Willi Clinics (see Services below for relevant providers)

When available, management at a PWS Clinic is preferred.

Eyes/Vision

Common visual problems in PWS include strabismus and myopia. Strabismus includes both esotropia, which is more common, and exotropia. Treatment may involve correction of refractive errors, patching of the better eye, and/or surgical correction of unbalanced eye muscles. Generally, treatment is more successful if started in the first few years of life. Amblyopia, or reduced vision due to disuse of an eye during development (commonly called "lazy eye"), results from inadequately treated strabismus.

Myopia (near-sightedness) and hyperopia (far-sightedness) are also common findings in children with PWS. Periodic screenings with a pediatric ophthalmologist are recommended throughout childhood.

Oculo-cutaneous albinism type 2 has been linked to the 15q11-q13 region - individuals with PWS due to a deletion in this area may also exhibit signs of depigmentation. Strabismus and impaired visual acuity may also be features of oculo-cutaneous albinism type 2. [Saadeh: 2007]

Subspecialist Collaborations & Other Resources

Pediatric Ophthalmology (see Services below for relevant providers)

Referrals to ophthalmology may be needed for management of strabismus and acuity problems beginning in early childhood.

Maturation/Sexual/Reproductive

Individuals with PWS typically have hypogonadotropic hypogonadism, resulting in decreased estrogen levels in females and decreased testosterone levels in males. In the newborn period, most males have small testes and scrotum. Undescended testes are common in PWS. If the testes are not palpable, referral for a testicular ultrasound and evaluation by a pediatric urologist should be made by about 6 months of age. In newborn females, labial hypoplasia has been reported.

Over 80% of adolescents and adults with PWS will experience incomplete sexual maturation. Some children show early growth of underarm and pubic hair, but then do not progress through puberty normally. Both sexes have good responses to treatment for hormone deficiencies, although side effects to treatment have been reported. Males with PWS typically do not progress past mid-puberty and make no mature sperm. Testosterone levels are usually low and testosterone replacement beginning early in adolescence is often helpful. Normal levels of testosterone are needed to preserve bone mass and prevent osteoporosis. Testosterone replacement also increases muscle mass and strength. In older males with a small penis, a short course of testosterone can be given to improve appearance and size.

Most females with PWS do not have regular menstrual cycles and if they do menstruate, may have early menopause. Hypoplasia of the labia and/or clitoris in teenage females is common. The use of estrogen replacement therapy for women with PWS is not well established, but may help preserve bone mass and reduce osteoporosis.

Fertility has only been documented in a few rare cases. Sexually active individuals should be counseled regarding the risk of pregnancy and the risk of having a child with PWS (50%, except when the mutation is due to maternal disomy).

Sexuality needs to be discussed with adolescents with disabilities and their parents in an effort to address common issues that may include:
  • the assumption that teens with disabilities do not need this information,
  • the lack of sex education specific to people with disabilities,
  • motor impairments that may make sexual function difficult, e.g., condom use,
  • the presence of intellectual impairment that might complicate the imparting and understanding of sex education material,
  • concerns about sexual exploitation in this population, and
  • body image concerns on the part of the adolescents.
See Sexuality and People with Disabilities (PDF Document 257 KB).

Subspecialist Collaborations & Other Resources

Pediatric Endocrinology (see Services below for relevant providers)

May be helpful for individuals with PWS with delayed puberty for consideration, initiation, and management of sex hormone therapy and for hypogonadism.

Gynecology (Ped/Adol, Special Needs) (see Services below for relevant providers)

To guide female patients with delayed puberty.

Pediatric Urology (see Services below for relevant providers)

For evaluation and management of males with crypto-orchidism and/or a small penis.

Dental

Referral to and regular follow-up by a dentist should be part of the overall treatment plan. However, providing preventive dental care may be difficult for the following reasons:
  • Cognitive and fine motor skills may limit the child's ability to perform brushing and flossing. Early emphasis on brushing and flossing is important.
  • Behavioral and health issues (e.g., sleep apnea, congenital heart disease) may increase the difficulty of dental visits and increase the risks of using sedation in the dental setting.
Children with PWS are prone to dental problems:
  • Soft dental enamel makes it easier for caries to develop. Special toothbrushes can be used that are less abrasive and help maintain the enamel and improve oral hygiene.
  • There is a tendency to grind teeth and sugar intake may be large.
  • Overproduction of saliva results in thick, crusted deposits in the corners of the mouth and difficulty with the saliva coating and protecting the teeth. Products to increase and somewhat thin the saliva are available.
The primary care provider's role should include:
  • Discussing the need for routine dental care with families and ensuring that the child and family have been instructed on dental hygiene and fluoride supplementation. The CDC's page My Water's Fluoride provides information about fluoride levels in local water sources.
  • Helping families identify an appropriate dentist and/or funding. Dental check-ups are recommended by age 1 and then every 6 months.
  • Offering the family information about dental care specific to PWS. Ensure that families and dental care providers are aware of medical issues that may impact care (e.g., need for bacterial prophylaxis and sedation risks).
  • Monitoring general oral hygiene and dental health at well-child visits and discussing issues with families as they arise. If signs of periodontal disease are evident, refer to a dental provider as-soon-as possible; periodontal disease can be rapidly progressive.
  • Helping the child, teen, and family manage halitosis, which may result in societal exclusion. It may improve with simple interventions such as tongue brushing, mouthwashes, breath fresheners, and better dental hygiene or may require evaluation for medical issues, including chronic sinusitis, gastro-esophageal reflux, drooling, and periodontal disease.

Subspecialist Collaborations & Other Resources

General Dentistry for Children (see Services below for relevant providers)

Particularly helpful when pediatric dentists are not available.

Pediatric Dentistry (see Services below for relevant providers)

Often have special interest and skill in the care of children with special health care needs.

Development (general)

Language: Speech and language skills of individuals with PWS vary greatly, ranging from nonverbal to normal skills in adulthood. For children with PWS, the development of speech and language is often delayed; sometimes children do not learn to combine words until they are 6 years old.. Problems are seen with speech rate, voice quality, and coordinating movements of the tongue, lips, jaws, and palate, which can lead to slow, slurred, and/or nasal speech. Most will have greater delays in expressive language, compared to receptive language. Difficulties with auditory short-term memory, order processing, and auditory verbal processing skills may affect vocabulary, grammar, and conversational abilities. Despite oral difficulties, children with PWS may show strengths in written language skills and reading, although reading comprehension may be poor. Speech and language difficulties continue into adolescence and adulthood. In these stages, emphasis should be placed on functional language skills and life-skills training. The Medical Home portal's Normal Pattern of Speech Development (general) issue page discusses normal language milestones.

Sign language, picture communication boards, and augmentative communication devices should be considered for individuals with verbal communication problems. Referrals should be made as early as possible to speech and language pathologists. Aiding communication may help with behavior problems. The Medical Home Portal's Augmentative Communication (general) issue page provides further information.

Subspecialist Collaborations & Other Resources

Speech/Language Therapy (see Services below for relevant providers)

In addition to speech/language therapy, speech therapists can initiate augmentative communication when needed.

Mental Health/Behavior

Behavioral issues often impact the child with PWS and their family more than any other aspect of the condition. Family support and anticipatory guidance for developmental delays and medical problems should be provided. Transitions and life changes are easier if the person with PWS is prepared for them, for example, by allowing the child with PWS to visit a new school and meet his/her prospective teachers. Children with PWS should have a clear idea of expectations and the limits set for them, including those related to participation in social activities and interactions with other children.

To avoid secondary behavioral issues, hyperphagia needs to be managed consistently by family, teachers, health care providers, and anyone who interacts with the child. Controlling both the quantity and types of food that are available is essential. Attempts to suppress appetite with medication have been unsuccessful; active research continues in this area. Conflicts related to food may lead to other behavioral problems. Aggressive behaviors or acting out can also be problematic.

Co-management with psychology and/or psychiatry may be important if simple measures are ineffective. The choice of psychotropic medication is the same as in typical patients with psychiatric diagnoses, but dosing should start low and be titrated upward based on response since many individuals with PWS respond unusually to medication.

Mood stabilizers have been used successfully for treating mood disorders and severe impulse control. Valproate and lithium are well tolerated at typical doses. Carbamazepine and oxcarbazepine should be used with care because of the increased risk for hyponatremia. Individuals with PWS will sometimes ingest large quantities of flavored beverages or water making them more susceptible to hyponatremia than non-PWS subjects.

Serotonin reuptake inhibitors have induced mood activation in some individuals with PWS causing worsening of behavioral problems or resulting in psychosis. The worsening behavior after an initial favorable response to medication may cause some physicians to increase the dose, which further complicates treatment. However, when monitored closely, this class of medications can effectively treat OCD and depression in individuals with PWS.

It is important to monitor all medications that may affect eating behavior and weight gain. In well-controlled environments, neuroleptics, atypical neuroleptics, valproic acid, and lithium have been used effectively without discernable change in food seeking behavior. [Forster: 2008] In severe cases, the child may need to be admitted to a facility that has experience in dealing with behavioral issues secondary to underlying medical problems.

Subspecialist Collaborations & Other Resources

Psychologist, Child-18 (see Services below for relevant providers)

Refer for help in managing the behavior problems of children with PWS and for family counseling.

Psychiatrist, Child-18 (see Services below for relevant providers)

Refer for help with severe behavior problems requiring medical treatment.

Learning/Education/Schools

Individuals with PWS typically have impaired cognitive functioning. IQ scores are generally in the range of mild to moderate intellectual disability although scores may range from normal to profound disability. The Medical Home Portal's Intellectual Disability module provides diagnoses and management information; Intellectual Disability - Classification and Psychometric Testing (general) provide further relevant details. The type of gene alteration causing the PWS plays a role in IQ score results - individuals with PWS due to uniparental disomy (UPD) have higher verbal than performance scores, while children with PWS due to deletions have higher performance scores. Children with UPD generally perform better than children with deletions and the size of the deletion correlates inversely with performance. Areas primarily affected include reading, spelling, and math. Short-term visual memory is often a weak area, whereas visual perception, organization, and puzzle solving are relative strengths. Children with PWS should have full psychological evaluations, including IQ and achievement, so that school and future planning can be optimized. An Individual Education Plan (IEP) should be initiated as early as possible. For more information, please see Education & Schools and Cognitive and Psychiatric Issues in Prader-Willi Syndrome.

Attention deficit hyperactivity disorder (ADHD) should be treated if present. Co-management with a child psychiatrist may be indicated if medication is required. The Portal's diagnosis and management module can be found at Attention Deficit Hyperactivity Disorder (ADHD).

Subspecialist Collaborations & Other Resources

Psychologist, Child-18 (see Services below for relevant providers)

For help with educational programming and for behavior management programs.

Neuropsychology (see Services below for relevant providers)

For evaluation and for help with educational programming.

Psychiatrist, Child-18 (see Services below for relevant providers)

For medication management of ADHD if needed.

Family

There are many demands on families of children and adults with PWS. The Medical Home, in addition to providing support for the child, can help families access emotional, financial, and informational resources. Referral to the Prader-Willi Syndrome Association (USA) for local information and support by other families may be invaluable. Family Support (PWSA USA) and Supplemental Security Income Guide for Children with PWS (PWSA) may also be helpful.

Transitions

Transitioning to adult life and health care systems can be challenging for individuals with PWS, their families, and their care providers. An important goal in transition planning is to find an acceptable medical home where the care provider recognizes the special needs of individuals with PWS and can communicate with the pediatric team. Other important goals of transition planning are to identify where the person will live and what the educational and vocational training needs are. Transition should include the following:
  • Planning should begin well before the patient will be transitioned.
  • Planning should take medical problems and learning disabilities into account.
  • Transition planning should center on the person and their family, and take into account cultural, ethnic, and spiritual values. Economic resources of the family need to be considered.
  • The overall goals of the youth should be considered. Goals for the future should include measurable outcomes. Transitions should be presented as positive changes in the person's life.
  • All members of the health care team, current and future, should agree on the overall plan and how to achieve the outcomes desired.
  • Medical management should be planned so there is no interruption in care and so that the patient and family are aware of potential changes in available resources. Medicaid support typically ends at age 19 and social security financial support after age 18.
  • Two key members of the transition team are 1) a nutritionist who is familiar with the unique problems of the condition and past management plans and 2) a social worker who can provide information about appropriate medical care and financial resources for adults.

Subspecialist Collaborations & Other Resources

Health Insurance/Funding, Transition (see Services below for relevant providers)

Provides lists of funding sources.

Frequently Asked Questions

Where can I find answers to some of the questions parents might have about PWS?

Answers to questions often asked by parents and other cargivers can be found on the Portal at Prader-Willi Syndrome.

What is the risk for other family members or future babies?

Most cases of PWS are sporadic; however, at least 20 families have been reported with more than one affected member, including reports in twins. The chance for familial recurrence is estimated to be less than 1%. However, this risk may be as high as 50% in some families where an imprinting defect causes defective control of differentially expressed genes in both the PWS child and the unaffected father.

Issues Related to Prader-Willi Syndrome

Resources

Information for Clinicians

Prader-Willi Syndrome Review (GeneReviews)
Detailed overview of Prader-Willi syndrome, testing, genetics, resources, reviews, and research; hosted by the National Center for Biotechnology Information.

Prader-Willi Syndrome (OMIM)
Extensive review of the literature, including clinical features and gene therapy; Online Mendelian Inheritance in Man, hosted by Johns Hopkins University.

Medical Issues A-Z (PWSA)
Links from this page include clinical content about: adrenal insufficiency, edema, intestinal issues, growth hormone, high pain threshold, hyperphagia, hypogonadism, hypothyroidism, nutrition, orthopedic issues, post-operative issues, psychotropic medications, medical alerts, respiratory issues, seizures, skin picking, and sleep problems; Prader-Willi Syndrome Association.

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome(PDF Document 170 KB)
International guideline from 2013; J Clin Endocrin Metab.

PWS Genetic Testing (GeneTests)
List of laboratories providing testing for PWS.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision and management guidelines, and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal & Child Health Bureau, and the American Academy of Pediatrics.

Helpful Articles

PubMed search on Prader-Willi syndrome: articles over the last 10 years

Butler MG.
Prader-Willi syndrome: obesity due to genomic imprinting.
Curr Genomics. 2011;12(3):204-15. PubMed abstract / Full Text

Butler MG, Lee PDK, Whitman, BY.
Management of Prader-Willi Syndrome.
3rd ed. New York, NY: Springer Verlag Inc.; 2006. 0387253971
Textbook with diagnosis and management information for PWS. Includes clinical, genetic, social, family, and community issues.

Butler MG, Roberts J, Hayes J, Tan X, Manzardo AM.
Growth hormone receptor (GHR) gene polymorphism and Prader-Willi syndrome.
Am J Med Genet A. 2013;161A(7):1647-53. PubMed abstract / Full Text

Cassidy SB, Schwartz S, Miller JL, Driscoll DJ.
Prader-Willi syndrome.
Genet Med. 2012;14(1):10-26. PubMed abstract / Full Text

Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS.
GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome.
J Clin Endocrinol Metab. 2013;98(6):E1072-87. PubMed abstract / Full Text

Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold JA, Kimonis V, Dykens E, Butler MG, Shuster JJ, Driscoll DJ.
Nutritional phases in Prader-Willi syndrome.
Am J Med Genet A. 2011;155A(5):1040-9. PubMed abstract / Full Text

Clinical Tools

Algorithms/Care Processes

Bowel Management Algorithm(PDF Document 47 KB)
Algorithm for management of chronic constipation developed in collaboration with pediatric gastroenterology.

Flowchart of Recommended Molecular Testing Strategy for PWS (AAP)
One-page flowchart from Health Supervision for Children With Prader-Willi Syndrome (figure 1).

Assessment Tools/Scales

Constipation Evaluation Tool(PDF Document 84 KB)
Provides a format for evaluation of chronic constipation in children.

Home Toileting Record(PDF Document 49 KB)
An easy-to-use form for keeping track of a child's toileting habits.

Care/Action Plans

Bowel Management (general)(PDF Document 74 KB)
General information on bowel function and management of constipation for families and providers.

Growth/BMI Charts

Growth Standards for Non-Growth Hormone Treated PWS (0-36 months) (AAP)
Curves for weight, length, head circumference, weight/length, and BMI for white infants (boys and girls) with PWS between 0 and 36 months of age. Link leads to free article by Butler et al. published in Pediatrics (2011). Scroll for charts, PowerPoint slide can be downloaded.

Growth Charts for Non-Growth Hormone Treated PWS (3-18 years) (AAP)
Curves for weight, height, head circumference, and BMI for white male and female U.S. subjects with PWS between 3 and 18 years of age. Link leads to article by Butler et al. published in Pediatrics (2015). Scroll for charts; PowerPoint slide can be downloaded. Accessible with subscription.

Information & Support for Families

Excellent resources, including those listed below, are available from the Prader-Willi Syndrome Association (USA). Medical home providers and families of children with PWS are encouraged to visit their web site and see the numerous resources available.

Family Diagnosis Page

Information on the Web

Prader-Willi Syndrome (Genetics Home Reference)
Information about PWS; sponsored by the National Library of Medicine.

Prader-Willi Syndrome (MedlinePlus)
Information about PWS and links to other reliable sources of information; sponsored by the National Library of Medicine

National Organization of Rare Disorders (NORD)
Provides information about many uncommon conditions, including rare "orphan" diseases, and links to organizations that provide services; National Organization for Rare Diseases.

Supplemental Security Income Guide for Children with PWS (PWSA)
Frequently asked questions and downloadable documents for preparing a Supplemental Security Income (SSI) form; Prader-Willi Syndrome Association.

Utah Prader-Willi Syndrome Association
Provides families and professionals with a network of support, resources, and information. Promotes awareness of PWS and raise funds that will directly benefit affected individuals in Utah.

Food and Behavior in PWS (Pittsburgh Partnership)
Information for providers and families regarding food security and other aspects of behavior in individuals with PWS

Support National & Local

Prader-Willi Syndrome Association (USA)
A strong national organization of families and professionals, PSWA offers a toll-free helpline, a bimonthly newsletter and numerous publications about PWS, an annual family conference and scientific meeting, and chapters throughout the country to provide local family support and advocacy.

Heartland Genetic Services Collaborative
Region 5 of the Genetic Service Collaboratives; provides information for families and providers including listings of local resources.

Studies/Registries

Angelman, Rett, and Prader-Willi Syndromes Research Consortium
An integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research in genetic and neurodevelopmental disorders and maintaining a Patient Contact Registry.

Prader-Willi Syndrome Studies (ClinicalTrials.gov)
List of studies related to PWS; a service of the U.S. National Institutes of Health.

Services for Patients & Families

Adult Genetics

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Behavioral Programs

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Cancer Genetic Counseling/Risk Assess

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Developmental Pediatrics

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Early Intervention Programs

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General Dentistry for Children

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Genetics Laboratories

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Group Homes

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Gynecology (Ped/Adol, Special Needs)

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Health Insurance/Funding, Transition

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Learning Evaluations, Counseling

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Neuropsychology

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Nutrition/Dietary

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Occupational Therapy

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Pediatric Cardiology

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Pediatric Dentistry

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Pediatric Dermatology

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Pediatric Endocrinology

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Pediatric Gastroenterology

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Pediatric Genetics

Pediatric Medical Genetics, more info...
81 N Mario Capecchi Drive
Eccles Primary Children's Outpatient Services Bldg.
Salt Lake City, UT 84113
Phone: 801-213-3599
Fax: 801-585-7252
http://medicine.utah.edu/pediatrics/genetics/

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Pediatric Ophthalmology

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Pediatric Orthopedics

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Pediatric Otolaryngology

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Pediatric Pulmonology

Pediatric Pulmonology, more info...
100 N Mario Capecchi Drive
Salt Lake City, UT 84133
Phone: 801-213-3599
http://healthcare.utah.edu/pediatrics/Pulmonary/index.php

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Prader-Willi Clinics

Prader-Willi Syndrome Clinic , more info...
44 N Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-712-0501
Toll Free Phone: 800-829-8200
http://www.health.utah.gov/cshcn/index.html

Prenatal Genetic Counseling/Diagnosis

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Psychiatrist, Child-18

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Psychologist, Child-18

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SSI, Supplemental Security Income

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Sleep Studies/Polysomnography

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Speech/Language Therapy

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Vocational Education

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Authors

Author: Merlin G. Butler, MD, PhD - 11/2014
Contributing Author: Jennifer Goldman-Luthy, MD, MRP, FAAP - 2/2015
Content Last Updated: 2/2015

Bibliography

Alexander RC, Greenswag LR, Nowak AJ.
Rumination and vomiting in Prader-Willi syndrome.
Am J Med Genet. 1987;28(4):889-95. PubMed abstract
A study that includes those with Prader-Willi who also experience more unusual symptoms of rumination and vomiting.

Butler MG.
Prader-Willi syndrome: current understanding of cause and diagnosis.
Am J Med Genet. 1990;35(3):319-32. PubMed abstract
Reviews of current understanding of the major clinical, cytogenetic, and DNA findings. Summarizes from literature clinical manifestations and cytogenetic abnormalities.

Butler MG.
Management of obesity in Prader-Willi syndrome.
Nat Clin Pract Endocrinol Metab. 2006;2(11):592-3. PubMed abstract / Full Text
Discusses pros and cons of various ways to treat obesity in Prader-Willi syndrome.

Butler MG.
Prader-Willi syndrome: obesity due to genomic imprinting.
Curr Genomics. 2011;12(3):204-15. PubMed abstract / Full Text

Butler MG, Lee J, Manzardo AM, Gold JA, Miller JL, Kimonis V, Driscoll DJ.
Growth charts for non-growth hormone treated prader-willi syndrome.
Pediatrics. 2015;135(1):e126-35. PubMed abstract / Full Text

Butler MG, Lee PDK, Whitman, BY.
Management of Prader-Willi Syndrome.
3rd ed. New York, NY: Springer Verlag Inc.; 2006. 0387253971
Textbook with diagnosis and management information for PWS. Includes clinical, genetic, social, family, and community issues.

Butler MG, Meaney FJ.
Standards for selected anthropometric measurements in Prader-Willi syndrome.
Pediatrics. 1991;88(4):853-60. PubMed abstract
Standards that can be used with the examination of patients who have Prader-Willi syndrome and in the comparison of the patient who has Prader-Willi syndrome with other similarly affected individuals. The standards may also be useful for assisting in the diagnosis of Prader-Willi syndrome, particularly in younger individuals.

Butler MG, Roberts J, Hayes J, Tan X, Manzardo AM.
Growth hormone receptor (GHR) gene polymorphism and Prader-Willi syndrome.
Am J Med Genet A. 2013;161A(7):1647-53. PubMed abstract / Full Text

Butler MG, Smith BK, Lee J, Gibson C, Schmoll C, Moore WV, Donnelly JE.
Effects of growth hormone treatment in adults with Prader-Willi syndrome.
Growth Horm IGF Res. 2013;23(3):81-7. PubMed abstract / Full Text
This is a study of 11 adults with PWS (6F:5M; average age=32 yrs) over a 2 year period with GH treatment during the first year only. Electrolytes, IGF-I, glucose, thyroid, insulin, lipids, body composition, physical activity and strength, diet, energy expenditure and quality of life data were collected and analyzed statistically using linear modeling at baseline, at 12 months following GH therapy and at 24 months after treatment cessation for 12 months. This study reports the beneficial effects of GH treatment in adults with PWS regarding body composition, physical activity and plasma HDL and IGF-I levels. Several beneficial effects diminished to near baseline after cessation of GH treatment for 12 months supporting the continuation of treatment in PWS into adulthood and possibly adults not previously treated during childhood.

Butler MG, Sturich J, Lee J, Myers SE, Whitman BY, Gold J, Kimonis V, Scheimann A, Terrazas N, Driscoll DJ. .
Growth Standards in Infants with Prader-Willi Syndrome.
Pediatrics. 2011;In press( Vol. 127 ):No. 4 April 1, 2011 . / Full Text
Standardized growth curves for weight, length, head circumference, weight/length, and BMI for non–growth hormone–treated white infants (boys and girls) with Prader-Willi syndrome (PWS) between 0 and 36 months of age.

Cassidy SB, Schwartz S, Miller JL, Driscoll DJ.
Prader-Willi syndrome.
Genet Med. 2012;14(1):10-26. PubMed abstract / Full Text

Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS.
GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome.
J Clin Endocrinol Metab. 2013;98(6):E1072-87. PubMed abstract / Full Text

Festen DA, de Weerd AW, van den Bossche RA, Joosten K, Hoeve H, Hokken-Koelega AC.
Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment.
J Clin Endocrinol Metab. 2006;91(12):4911-5. PubMed abstract
A study showing GH treatment does not aggravate the sleep-related breathing disorders in young PWS children and that monitoring during upper respiratory tract infection in PWS children should be considered.

Forster, JL, and Gourash, LM.
Managing Prader-Willi Syndrome: A Primer for Psychiatrists .
2008; MD Pittsburgh Partnership Printed by Prader-Willi Syndrome Association USA ; http://www.pwsausa.org/syndrome/psychiatrists%20primer%20for%20pws.pdf
Discusses five domains of behavioral symptoms, and psychiatric evaluation, management, co-morbidity, and food security.

Goldberg DL, Garrett CL, Van Riper C, Warzak WJ.
Coping with Prader-Willi syndrome.
J Am Diet Assoc. 2002;102(4):537-42. PubMed abstract
Includes basic behavior-management strategies, including successful use of incentives, responding to misbehavior, rewarding compliance with an exercise program, and modifying the behavior management when indicated.

Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M.
Recommendations for the diagnosis and management of Prader-Willi syndrome.
J Clin Endocrinol Metab. 2008;93(11):4183-97. PubMed abstract / Full Text
Based on published evidence-based data, unpublished data from personal experience, previous National and International PWS Conferences, and Prader-Willi Syndrome Association (USA) Clinical Advisory Groups. Written by an open international multidisciplinary expert group that met in 2006.

Gunay-Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB.
The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria.
Pediatrics. 2001;108(5):E92. PubMed abstract / Full Text
Suggestions for revised clinical criteria to help identify the appropriate patients for DNA testing for PWS.

Haqq AM, Stadler DD, Jackson RH, Rosenfeld RG, Purnell JQ, LaFranchi SH.
Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome.
J Clin Endocrinol Metab. 2003;88(5):2206-12. PubMed abstract
Contains results of a study on the effects of GH administration on pulmonary function, sleep, behavior, cognition, linear growth velocity, body composition, and resting energy expenditure (REE) in children with Prader-Willi syndrome.

Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg F.
Prader-Willi syndrome: consensus diagnostic criteria.
Pediatrics. 1993;91(2):398-402. PubMed abstract
Two scoring systems are provided: one for children aged 0 to 36 months and another one for children aged 3 years to adults. Intended to aid in recognition of the syndrome in hypotonic infants and in obese, mildly retarded, behaviorally disturbed adolescents and adults.

Holm VA, Pipes PL.
Food and children with Prader-Willi syndrome.
Am J Dis Child. 1976;130(10):1063-7. PubMed abstract
Illustrates successes in preventing excessive weight gain in children with PW when caretakers receive appropriate counseling on how to provide low-calorie food and how to make other food inaccessible.

Kroonen LT, Herman M, Pizzutillo PD, Macewen GD.
Prader-Willi Syndrome: clinical concerns for the orthopaedic surgeon.
J Pediatr Orthop. 2006;26(5):673-9. PubMed abstract
Cites osteopenia, poor impulse control and defiant behaviors, and diminished pain sensitivity as aspects of PWS that may complicate all facets of orthopaedic nonsurgical and surgical management in this patient population.

McCandless SE.
Clinical report—health supervision for children with Prader-Willi syndrome.
Pediatrics. 2011;127(1):195-204. PubMed abstract / Full Text
Designed to assist the pediatrician in caring for children with Prader-Willi syndrome diagnosed by clinical features and confirmed by molecular testing.

Miller J, Kranzler J, Liu Y, Schmalfuss I, Theriaque DW, Shuster JJ, Hatfield A, Mueller OT, Goldstone AP, Sahoo T, Beaudet AL, Driscoll DJ.
Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.
J Pediatr. 2006;149(2):192-8. PubMed abstract

Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold JA, Kimonis V, Dykens E, Butler MG, Shuster JJ, Driscoll DJ.
Nutritional phases in Prader-Willi syndrome.
Am J Med Genet A. 2011;155A(5):1040-9. PubMed abstract / Full Text

Saadeh R, Lisi EC, Batista DA, McIntosh I, Hoover-Fong JE.
Albinism and developmental delay: the need to test for 15q11-q13 deletion.
Pediatr Neurol. 2007;37(4):299-302. PubMed abstract / Full Text
Reports that Phenotypic features of Angelman syndrome or Prader-Willi syndrome in a patient with albinism should prompt further gene testing.

Scheimann AO, Butler MG, Gourash L, Cuffari C, Klish W.
Critical analysis of bariatric procedures in Prader-Willi syndrome.
J Pediatr Gastroenterol Nutr. 2008;46(1):80-3. PubMed abstract
Various bariatric procedures have been used to cause gastric stasis, decrease gastric volume, and induce malabsorption, with poor results in PWS patients in comparison with normal obese individuals.

Shapira NA, Lessig MC, Murphy TK, Driscoll DJ, Goodman WK.
Topiramate attenuates self-injurious behaviour in Prader-Willi Syndrome.
Int J Neuropsychopharmacol. 2002;5(2):141-5. PubMed abstract
Report attenuation of SIB with resultant lesion healing in three PWS adults treated with topiramate in an 8-wk open-label trial - suggest more study is needed.

Sone S.
Muscle histochemistry in the Prader-Willi syndrome.
Brain Dev. 1994;16(3):183-8. PubMed abstract
Although muscle hypotonia in PWS has been thought to be due to central nervous system abnormality, findings suggest that primary muscle pathology, including muscle fiber immaturity and abnormal muscle fiber type distribution, at least in part, plays a role in muscle hypotonia and weakness.

Stevenson DA, Anaya TM, Clayton-Smith J, Hall BD, Van Allen MI, Zori RT, Zackai EH, Frank G, Clericuzio CL.
Unexpected death and critical illness in Prader-Willi syndrome: report of ten individuals.
Am J Med Genet A. 2004;124A(2):158-64. PubMed abstract
Suggests that increased risk for critical illness be considered in the discussion of anticipatory guidance for the care of infants with PWS. Data showed that under the age of 2 years, childhood illnesses in general were associated with high fever and rapid demise or near-demise.

Wigren M, Hansen S.
ADHD symptoms and insistence on sameness in Prader-Willi syndrome.
J Intellect Disabil Res. 2005;49(Pt 6):449-56. PubMed abstract
Results showed that indices of ADHD and excessive insistence on sameness were common.

de Lind van Wijngaarden RF, Otten BJ, Festen DA, Joosten KF, de Jong FH, Sweep FC, Hokken-Koelega AC.
High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome.
J Clin Endocrinol Metab. 2008;93(5):1649-54. PubMed abstract / Full Text
Investigates whether PWS patients suffer from central adrenal insufficiency (CAI) during stressful conditions. Based data, recommends considering treatment with hydrocortisone during acute illness in PWS patients unless CAI has recently been ruled out with a metyrapone test.