Prader-Willi Syndrome - Description

Page Contents

• Other Names
• ICD-9
• Description
• Genetics
• Prognosis
• Prevalence
• Pearls And Alerts
• Helpful Articles

Other Names

Prader-Labhart-Willi syndrome

ICD-9

759.81, Prader-Willi syndrome

Description

Prader-Willi syndrome (PWS) is the most common genetically-identified cause of life-threatening obesity in humans. 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; and
• sticky saliva;

Those with PWS and the 15q11-q13 deletion may also have hypopigmentation relative to family background.

Please see the Treatment section and Multi-disciplinary management for PWS Issue Page for details on necessary evaluations for children with this disorder.

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. See Imprinting (GeneTests) for more information.

See Prader-Willi syndrome genetics Issue Page for more information.

See Prader-Willi Syndrome Review (GeneReviews) and Chromosome 15 in PWS (PWSA USA) for more information.

Prognosis

If obesity is avoided and complications are well managed, life expectancy for individuals with PWS is normal or near-normal. [Butler: 2006] Most individuals with this syndrome can lead healthy lives if diagnosed early and a treatment plan is put in place to avoid the complications of uncontrolled obesity. Early education of caregivers and the institution of a controlled environment are essential to a good outcome.

Prevalence

Estimates of the prevalence of PWS range from 1/8,000 to 1/20,000 individuals. 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 is reported disproportionately in Caucasians. [Butler: 2006]

Pearls And Alerts

Helpful Articles

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

Bittel DC, Butler MG.
Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology.
Expert Rev Mol Med. 2005;7(14):1-20. PubMed abstract
Overview of the syndrome, genetic causes, and research.

Butler MG, Lee PDK, Whitman, BY; ed.
Management of Prader-Willi Syndrome.
3rd ed. New York, NY: Springer Verlag Inc.; 2006. 0387253971
Overview of the syndrome and natural history; diagnosis and genetics; medical physiology; and treatment and multidisciplinary management.

Butler MG.
Management of obesity in Prader-Willi syndrome.
Nat Clin Pract Endocrinol Metab. 2006;2(11):592-3. PubMed abstract

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
Written by an open international multidisciplinary expert group that met in October 2006 in France with 37 invited speakers/session chairs and 85 additional participants. The guidelines were developed from published evidence-based data, unpublished data from personal experience, previous National and International PWS Conferences and Prader-Willi Syndrome Association (USA) Clinical Advisory Groups.

Cassidy SB, Driscoll DJ.
Prader-Willi syndrome.
Eur J Hum Genet. 2009;17(1):3-13. PubMed abstract

Butler MG.
Prader-Willi syndrome: current understanding of cause and diagnosis.
Am J Med Genet. 1990;35(3):319-32. PubMed abstract

Butler MG, Lee PDK, Whitman BY.
Management of Prader-Willi Syndrome.
3rd ed ed. New York, NY: Springer-Verlag Publisher; 2010.

Prader-Willi Syndrome Module Authors

The authors listed above are responsible for the overall Prader-Willi Syndrome Module. Authors contributing to individual pages in the module are listed on those pages.

Funding/Support

This module was developed in partnership with the Heartland Regional Genetics and Newborn Screening Collaborative Heartland Regional Genetics and Newborn Screening Collaborative and was funded in part by a Health Resources Services Administration (HRSA) cooperative agreement (U22MC03962).

We appreciate the Prader-Willi Syndrome Association (USA) for their outstanding support of individuals with PWS and their families and for the information they provide on their website – www.pwsausa.org – to which we have provided several links within the Diagnosis Module.

Page Bibliography

Butler MG.
Management of obesity in Prader-Willi syndrome.
Nat Clin Pract Endocrinol Metab. 2006;2(11):592-3. PubMed abstract