HEALTH WATCH TABLE — Prader-Willi Syndrome (PWS)

Considerations Recommendations
1. Head, eyes, ears, nose, throat
  • Children: Strabismus and myopia are common
  • Arrange an auditory brainstem response (ABR) in newborns
  • Undertake ophthalmology evaluation before 2 years of age, with particular attention to strabismus and visual acuity
  • Adults: Visual acuity is more commonly diminished than in the general population
  • Perform office-based screening of vision annually as recommended for average-risk adults, and when symptoms or signs of visual problems are noted, including changes in behavior and adaptive functioning.
  • Refer for vision assessment to detect glaucoma and cataracts every 5 years after age 45
2. Dental
  • Children: Decreased and sticky saliva flow can predispose to dental caries
  • Delays in teeth eruption and dental overcrowding may occur
  • Attend to oral hygiene in infants and children including use of soft foam toothbrushes, as well as dental products (toothpaste, sugarless gums, mouthwash) to stimulate saliva production
  • Arrange regular dental visits with particular attention to crowding of teeth and dental caries
  • Make orthodontic referral, as necessary
3. Cardiovascular
  • Adults: Cor pulmonale is a commonly reported cardio-vascular complication in those who are obese or have significant obstructive sleep apnea (OSA)
  • Cardiopulmonary compromise related to obesity is a common cause of death
  • Hypertension is frequently reported but is uncommon in children
  • When any risk factor is present, screen for cardiovascular disease earlier and more regularly than in the general population and promote prevention (e.g., increasing physical activity, reducing smoking)
  • Arrange cardiac evaluation, including cardiology consultation, for severely obese patients.
  • Manage underlying obesity (see below)
4. Respiratory
  • Children: Unexpected death may be caused by respiratory obstruction early in growth hormone therapy
  • Upper respiratory tract infections may affect some children and adults significantly.
  • Refer to ENT for evaluation for removal of tonsils/adenoids, if obstruction is present
  • All patients with PWS who have an upper respiratory tract infection or other respiratory symptoms should be assessed as soon as possible
  • Ascertain a sleep history and then arrange a sleep study before anesthesia, and if evidence of respiratory distress, sleep apnea, or obesity is present
  • Adults: Cardiopulmonary compromise is the most common cause of death
  • Ascertain a sleep history with attention to sleep disorders, obesity of any level, snoring, asthma, respiratory infections, and excessive daytime sleepiness
  • Consider cardiology or pulmonary referral, as needed
5. Sleep
  • Children: At risk for sleep-disordered breathing
  • Arrange routine sleep studies during infancy and childhood, and before starting growth hormone therapy and three months after initiating therapy
  • Ascertain a sleep history and arrange a sleep study before use of anesthesia, and if evidence of respiratory distress, sleep apnea or obesity is present.
  • Children and Adults: Narcolepsy/cataplexy is common than in the general population
  • At risk for sleep paralysis upon falling asleep or awakening, which may include hallucinations
  • Adults: Continue to be at risk for sleep-disordered breathing
  • Evaluate for daytime sleepiness or loss of muscle tone provoked by excitement or other strong emotions
  • Ascertain a sleep history, with attention to sleep disorders, obesity, snoring, asthma, respiratory infections, and excessive daytime sleepiness
  • Consider a sleep study, pulmonolgy, and ENT referral, as indicated
6. Gastrointestinal & nutrition
  • Children: Early concerns include gastroesophageal reflux disease (GERD) and reduced intake due to poor sucking
  • Failure to thrive is common in infancy followed by the development of hyperphagia and obesity in early childhood
  • ~10% develop gall bladder stones
  • Gastroparesis is common
  • Ascertain a comprehensive GI and nutrition history
  • Undertake video swallow in neonates based on clinical concerns
  • Attend to feeding ability and need for assisted feeding
  • Educate caregivers regarding the necessity of a lower-calorie regime, and environmental controls to prevent ready access to food
  • Attend to diet, nutrition, physical activity, and obesity, including plotting weight on standard growth charts
  • Refer to a dietitian/physician with experience in PWS, if possible, to develop an appropriate nutrition and food security regime
  • Refer to a gastroenterologist, nutritionist, or dietician, as appropriate. Behavioral management programs should be instituted
  • Adults: Obesity is common without a nutrition and food security program
  • Vomiting often reflects very serious illness (e.g., gastric necropsy)
  • Gastroparesis is common
  • Anal picking is common and may lead to colonic tears/bleeding
  • Constipation due to hypotonia is common
  • Ascertain a comprehensive GI and nutrition history. Attend to diet, nutrition, and obesity. Refer to a gastroenterologist, dietitian/physician with experience in PWS. Implement the modified Red, Yellow, Green (RYG) 2 diet based on energy requirements (ideally measured by indirect calorimetry) and food security programs
  • Behavioral management should be maintained with the assistance of a behavioral specialist
  • In the event of emesis history, the adult with PWS requires immediate evaluation and possibly medical imaging
  • Recommend daily multivitamins
  • Provide usual interventions to prevent and manage constipation
7. Genitourinary
  • Children: 80% - 90% of males have cryptorchidism
  • Precocious adrenarche may occur
  • Delayed and incomplete pubertal development is common in both sexes
  • Verify testicular descent before 2 years of age
  • Refer to a urologist for cryptorchidism (i.e., absence of one or both testes from the scrotum)
  • Consider referral to an endocrinologist or gynecologist/urologist, as appropriate, regarding hormone replacement therapy (HRT)
  • Adults: Incomplete pubertal development is common in both sexes
  • Refer to gynecologist/urologist, as indicated by clinical findings, and for guidance regarding HRT for both sexes
8. Sexual function
  • Adults: Males and most females are infertile
  • Pregnancy, though unlikely, has been reported
  • Educate and, if sexually active, counsel
  • Consider contraception in women who menstruate
9. Musculoskeletal
  • Children: 30% - 70% have scoliosis
  • 10% have hip dysplasia
  • Prevention of osteoporosis should start at an early age
  • Assess for hip dysplasia in early infancy and before 2 years of age
  • Evaluate for scoliosis from infancy
  • Monitor with X-rays and refer to an orthopedic surgeon as necessary (Timing of surgical interventions are influenced by the severity of scoliosis and the degree of skeletal maturation)
  • Ensure adequate intake of calcium and vitamins D3 and K from childhood
  • Encourage a weight-bearing exercise program
  • Adults: Scoliosis and osteopenia/osteoporosis are common in both sexes.
  • Kyphosis may also occur
  • Screen for scoliosis and kyphosis with spinal X-rays and refer to an orthopedic surgeon as necessary
  • Assure adequate calcium and vitamins D3 and K intake
  • Screen for osteoporosis with regular bone mineral density tests
  • Refer to an endocrinologist for consideration of sex-hormone therapy to promote bone health
10. Neurology
  • Children: Hypotonia is common and leads to impaired or absent swallowing and sucking reflexes
  • Hypotonia gradually improves over time
  • 10% have epilepsy
  • All have some degree of cognitive impairment
  • Undertake clinical evaluation with attention to reduced motor activity and psychomotor delay
  • Consult relevant specialists as indicated by clinical findings
  • Treat epilepsy as in general population
11. Behavioral/mental health
  • Children & Adults: Severe skin picking is common and tends to increase with age
  • Severe maladaptive behaviors are common (including obsessive-compulsive disorders).
  • Psychosis may occur in adolescents and adults. Some features of PWS (e.g., tantrums, aggression, compulsivity, anxiety and mood disorder) may be treated with specific pharmacological agents
  • Risperidone, if indicated, does not usually lead to additional weight gain
  • Examine skin for evidence of severe skin picking, edema and skin breakdown
  • A behavior management program is required to support their dietary requirements. Avoid food-related occupational and educational activities. Refer to a psychologist or psychiatrist familiar with PWS when necessary to assist in distinguishing between behavior problems and psychiatric illness
12. Endocrine 
  • Children: Hypothyroidism, diabetes mellitus (Type II), growth hormone (GH) and sex hormone deficiencies may occur
  • Growth hormone therapy and strict dietary modifications can normalize body habitus
  • 60% can develop central adrenal insufficiency 3
  • Arrange for a PWS pediatric endocrinologist to assess for GH therapy as soon as diagnosis is confirmed. An orthopedic surgery referral may also be indicated before GH treatment is started
  • Make ENT referral to evaluate upper airway with regards to enlarged tonsils and adenoids prior to starting GH therapy
  • Screen before and during GH replacement for hypothyroidism, diabetes, and scoliosis. (See No. 4 Respiratory and No. 5 Sleep sections for other recommended assessments prior to GH replacement)
  • Beginning at age 2, assess obese children for diabetes mellitus (Type II)
  • Refer to an endocrinologist as appropriate for consideration of sex-hormone replacement therapy (See No. 7 Genitourinary above)
  • Undertake cortisol evaluation for all children
  • Adults: As per children, growth and sex hormone deficiencies continue to be found
  • Growth hormone therapy in adults can help to prevent obesity and improve strength and endurance
  • Undertake clinical assessment with attention to thyroid function, diabetes mellitus (Type II), and hypogonadism
  • Refer to an endocrinologist, as appropriate, including for consideration of GH and sex-hormone therapy
13. Other
  • Molecular causes of PWS differ (e.g., in order of frequency: deletion, uniparental disomy, imprinting errors) each of which effect recurrence risks and possible clinical manifestations
  • Refer to a genetics clinic for evaluation and counseling, where appropriate

Original tool: © 2011 Surrey Place Centre.
Developed by Forster-Gibson C, Berg J, & Developmental Disabilities Primary Care Initiative Co-editors.

Expert Clinician Reviewers
Thanks to the following clinicians for their review and helpful suggestions.

  • Karen Balko, RD
    Coordinator of Prader-Willi Syndrome Clinic, North York General Hospital
    Toronto, Ontario
  • Glenn Berall, MD
    Chief of Pediatrics, North York General Hospital
    Toronto, Ontario
  • Suzanne B. Cassidy, MD
    Clinical Professor of Pediatrics,
    Division of Medical Genetics
    University of California, Irvine, California

Modified with permission of Surrey Place Centre. This tool was reviewed and adapted for U.S. use by physicians on the Toolkit’s Advisory Committee; for list, view here.

Additional reviewer was Elizabeth Roof, MA, Senior Research Specialist, Prader-Willi and Williams Syndrome Research Projects, Vanderbilt Kennedy Center, Nashville, TN.

Resources

References

  1. Sullivan WF, Berg JM, Bradley E, Cheetham T, Denton R, Heng J, Hennen B, Joyce D, Kelly M, Korossy M, Lunsky Y, McMillan S. Primary care of adults with developmental disabilities: Canadian consensus guidelines. Can Fam Physician 2011;57:541-53.
  2. Balko K. Red yellow green: system for weight management. Toronto: Ontario Prader-Willi Syndrome Association; 2005.
  3. de Lind van Wijngaarden RF, Otten BJ, Festen DA, Joosten KF, de Jong FH, Sweep FC, et al. High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome. J Clin Endocrinol Metab. 2008 May;93(5):1649-54.

Other references consulted:

  • Deal CL. Tony M. Hoybye C. Allen DB. Tauber M. Christiansen JS. 2011 Growth Hormone in Prader-Willi Syndrome Clinical Care Guidelines Workshop Participants.  Journal of Clinical Endocrinology & Metabolism. 2013 June; 98(6):E1072-87.