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Prader-Willi Syndrome

Background
Medical Management Considerations
References
Resources for Families
Advisory Committee
Publication Information

Learning Points

  • Recognize that Prader-Willi Syndrome is a neurobehavioral genetic disorder resulting from one of three genetic causes.
  • Restate the occurrence of Prader-Willi Syndrome (1:5,000 to 1:10,000).
  • Select the optimal laboratory technique for diagnosing Prader-Willi Syndrome (DNA probe analysis, when available) and explain why it is superior to other available tests (DNA probe analysis can recognize uniparental disomy).
  • Confirm that Prader-Willi Syndrome and Angelman Syndrome share a similar genetic basis.
  • List six characteristic features of Prader-Willi Syndrome; e.g.,
    • Incomplete sexual development in puberty
    • Obesity beginning in early childhood
    • Insatiable overeating and desire for food (resistant to diet and behavior modification)
    • Impulsive, stubborn and perseverative behavior
    • Skin picking
    • Decreased sensitivity to pain
  • Acknowledge that many of the common conditions associated with Prader-Willi Syndrome are secondary results of obesity and, therefore, may be preventable.
  • Restate the main focus of medical management of Prader-Willi Syndrome (maintaining a strict diet of regular, balanced meals).
  • Recommend that siblings, extended family members, neighbors, friends, educators and all other caregivers receive appropriate education and counseling regarding food restriction and the child’s diet.
  • Refer families to appropriate resources on Prader-Willi Syndrome.

BACKGROUND
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Description and Cause

Prader-Willi Syndrome is a neurobehavioral genetic disorder resulting from one of three genetic causes: (1) a paternal deletion on the long arm of chromosome 15 in 70% of cases; (2) uniparental disomy (both chromosomes 15 of maternal origin) 15 in 25% of cases; or (3) an imprinting defect in 5% of cases. (Note: Angelman Syndrome is often discussed with Prader-Willi Syndrome because they share a similar genetic basis; return to the index to view a document on Angelman Syndrome.)

Diagnosis

Diagnosis is by chromosomal fine structural analysis, fluorescent antibody in situ hybridization (FISH), or DNA probe. DNA probe analysis, where available, is the technique of choice and is required in order to recognize uniparental disomy.

Occurrence

  • 1:10,000 to 1:5,000
  • Recurrence risk: 0.1%

Characteristic Features

  • Profound hypotonia in infancy
  • Feeding difficulties and failure to thrive in infancy
  • Poor body temperature control
  • Short stature
  • Small hands and feet (apparent in childhood)
  • Thin upper lip and downturned corners of the mouth
  • Almond-shaped eyes
  • Narrow bifrontal diameter (forehead)
  • Hypgonadism (underdeveloped genitalia)
  • Incomplete sexual development in puberty
  • Obesity beginning in early childhood
  • Insatiable overeating and desire for food (resistant to diet and behavior modification)
  • Impulsive, stubborn and perseverative behavior
  • Skin picking
  • Decreased sensitivity to pain
  • Delayed motor development
  • Speech delay
  • Mild to moderate mental retardation; range of cognitive functioning from low average with learning difficulties to severe mental retardation

Common Associations

Note: Many of these associations are secondary results of obesity and, therefore, may be preventable.

  • Scoliosis
  • Type II diabetes mellitus in second decade
  • Pulmonary hypertension
  • Pulmonary hypoventilation
  • Pickwickian syndrome
  • Cor pulmonale
  • Sleep apnea
  • Skin sores
  • Arteriosclerotic heart disease
  • Osteoporosis
  • Attention deficit disorder
  • Premature death

MEDICAL MANAGEMENT CONSIDERATIONS
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Note: These considerations are in addition to the normal medical care provided to an individual without Prader-Willi Syndrome. All recommendations can be addressed through clinical examination by the primary care provider, unless otherwise noted.

General physical health usually remains good in persons with Prader-Willi Syndrome unless obesity becomes severe. Typically, the focus of medical management is on maintaining a strict diet of regular, balanced meals. Food restriction can be very challenging and may impact the entire family system. Siblings, extended family members, neighbors, friends, educators and all other caregivers must receive appropriate education and counseling regarding food restriction and the child’s diet. The need to restrict and/or lock food may complicate family interactions and activities, and may cause stress for everyone involved. Siblings may require special support and counseling to help them understand and adjust to these issues.

Ongoing (all ages)

  • Recommend a strict diet of regular, balanced meals, making sure caloric intake does not exceed energy requirements (PWS children require fewer calories than normal children)
  • Recommend consultation by a registered dietician or nutritionist
  • Monitor weight and height using a PWS growth chart; compare to familial stature
  • Encourage parents to make sure the child cannot access extra food (teachers and other care providers must be informed also)
  • Implement applied behavior analysis to manage behavioral problems such as dietary management or skin picking
  • Monitor for sleep apnea / sleep disordered breathing

Infancy (Birth to 1 year)

  • Perform complete physical and neurological exam to detect congenital anomalies; screen for strabismus
  • Consider surgical correction of cryptorchidism
  • Consider physical/occupational therapy evaluation to address motor delay or feeding difficulties; special nipples may be needed
  • Ensure adequate nutrition, especially dietary fat intake
  • Refer to early intervention programs and
  • Prader-Willi/disability support groups
  • Provide genetic counseling, including a discussion of recurrence risk
  • Discuss possibility of SSI enrollment

Early Childhood (1 to 5 years)

  • Watch for hyperthermia or hypothermia
  • Screen for scoliosis regularly
  • Screen for strabismus
  • Recommend supplemental vitamins
  • If poor linear growth, test for growth hormone deficiency
  • Refer to early intervention program for evaluation and treatment recommendations
  • Recommend and arrange for dental care
  • Physical/occupational therapy evaluation & treatment, if indicated
  • Emphasize the need for strictly enforced rules and limits by all care providers
  • Consider referral to pediatric endocrinologist for testosterone injections to increase penile size for independent toileting and assessment for growth hormone therapy

Late Childhood (5 to 13 years)

  • Recommend supplemental vitamins and minerals, especially calcium
  • If poor linear growth, test for growth hormone deficiency
  • Recommend 20-30 minutes daily exercise
  • Screen for scoliosis regularly
  • Monitor school progress
  • Monitor speech and language progress
  • Try to maintain BMI < 30
  • Monitor for sleep apnea
  • Monitor for diabetes mellitus

Adolescence and Adulthood (13 years and over)

  • Recommend 20-30 minutes daily exercise
  • Recommend supplemental vitamins and minerals, especially calcium
  • Monitor for increasing behavioral problems
  • Monitor for decline in cognitive function, school progress & interventions
  • Discuss long-term financial plans
  • Discuss alternative community living resources
  • Discuss community-supported employment opportunities
  • Monitor prevocational training and vocational activities
  • Monitor for osteoporosis
  • Monitor for sleep apnea

REFERENCES
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Peer-reviewed Journal Articles/Academies

Greaves, N. et al. (2006). Repetitive and Ritualistic Behavior in Children with Prader-Willi Syndrome and Children with Autism. Journal of Intellectual Disability Research, 50, 92-100.

Hanchett, J., Greenswag, L. (1998). Health Care Guidelines for Individuals with Prader-Willi Syndrome. The Scientific Advisory Board of the Prader-Willi Syndrome Association. Retrieved April 18, 2006.

Hoffman, C.J, et al. (1992). A Nutrition Survey of and Recommendations for Individuals with Prader-Willi Syndrome Who Live in Group Homes. Journal of the American Dietetic Association 92(7), 823-830.

Ince, E. et al (2005). Characteristics of Hyperthermia and its Complications in Patients with Prader-Willi Syndrome, Pediatrics International, 47(5), 550-553.

Marin, A. et al. (1998). Prader-Willi Syndrome. American Journal of Psychiatry, 155(9), 1265-1273.

Miller, J. et al. (2005). Short-term Effects of Growth hormone on Sleep Abnormalities in Prader-Willi Syndrome. Journal of Clinical Endocrinology and Metabolism. 91(2), 413-417.

O’ Donoghue, F.J. et al. (2005). Sleep-Disordered Breathing in Prader-Willi Syndrome and its Association with neurobehavioral abnormalities. The Journal of Pediatrics, 147, 823-829.

Pavone, M. et al. (2006). Adenotosillectomy for Obstructive Sleep Apnea in Children with Prader-Willi Syndrome, Pediatric Pulmonology, 41, 74-79.

Riedl, S. et al. (2000). Death in Two female Prader-Willi Syndrome Patients during the Early Phase of Growth Hormone Treatment. Acta Paediatrica, 94(7), 974-977.

Tu, J. et al. (1992). Psychopharmacogenetic Aspects of Prader-Willi Syndrome. Journal of the American Academy of Child and Adolescent Psychiatry, 31(6) 1137-1140.

Wattendorf, D.J., Muenke, M. (2005). Prader-Willi Syndrome. American Academy of Family Physician, 72(5), 827 830.

Wodarski, L.A., et al. (1988). Interdisciplinary Case Management: A Model for Intervention for a Patient with Prader-Willi Syndrome. Journal of the American Dietetic Association, 88(3), 332-335.

Carrel, A.L. et al. (2002) Benefits of Long-term Growth Hormone Therapy in Prader-Willi Syndrome: A 4 year study. Journal of Clinical Endocrinology & Metabolism, 87, 581-1585

Special Interest Groups/Other Publications

Batshaw, M.L., Perret, Y.M. (1992). Children with Disabilities. Baltimore: Paul H. Brookes Publishing.

Cassidy, S.B. (2005). Prader-Willi Syndrome. In Cassidy, S.B., Allanson, J.E. (eds.) Management of Genetic Syndromes (2nd ed., pp. 429-480) New York: John Wiley & Sons.

Capute, A.J., Accardo, P.J. (1996). Developmental Disabilities in Infancy and Childhood vol. I: Neurodevelopmental Diagnosis and Treatment. Baltimore: Paul H. Brookes Publishing.

Capute, A.J., Accardo. P.J. (1996). Developmental Disabilities in Infancy and Childhood vol. II: The Spectrum of Developmental Disabilities. Baltimore: Paul H. Brookes Publishing.

Dambro, M.R. (1999). Griffith’s 5 Minute Clinical Consult. Baltimore: Lippincott Williams & Wilkins, p. 1218.

Greenswag, L.R., Alexander R.C. (1995). Management of Prader-Willi Syndrome (2nd Ed.) New York: Springer-Verlag.

Hagerman, R.J. (1999). Angelman Syndrome and Prader-Willi Syndrome. In Neurodevelopmental Disorders: Diagnosis and Treatment (pp. 243-290). New York: Oxford University Press.

Rubin, I. Leslie and Allen C. Crocker. 1989. Developmental Disabilities: Delivery of Medical Care for Children and Adults. Philadelphia: Lea & Febiger.

RESOURCES FOR FAMILIES
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California Department of Developmental Services
916-654-1690

California Regional Centers
916-654-1958

Genetests – Funded by the National Institutes of Health

Exceptional Parent Magazine
800-247-8080

March of Dimes Birth Defects Foundation
914-428-7100

Prader-Willi California Foundation
800-400-9994

The Prader-Willi Connection
800-358-0682

The Prader-Willi Foundation, Inc.
516-621-2445

Prader-Willi Syndrome Association (USA)
800-926-4797

ADVISORY COMMITTEE
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Theodore A. Kastner, M.D., M.S.
Felice Weber Parisi, M.D., M.P.H.
Robin L. Hansen, M.D.
Joan M. Reese, M.D., M.P.H.

PUBLICATION INFORMATION
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This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to California Department of Developmental Services.