Prader-Willi syndrome

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Prader-Willi syndrome
Classification and external resources
Template:Px Patient with the syndrome showing characteristic facial appearance, with elongated face, prominent nose, and smooth Philtrum
ICD-10	Q871
ICD-9	759.81
OMIM	176270
DiseasesDB	10481
eMedicine	ped/1880
MeSH	D011218

Prader-Willi Syndrome is a genetic disorder in which seven genes (or some subset thereof) on chromosome 15 are missing or unexpressed (chromosome 15q partial deletion) on the paternal chromosome. It was first described in 1956 by Andrea Prader, Heinrich Willi, Alexis Labhart, Andrew Ziegler, and Guido Fanconi of Switzerland. The incidence of PWS is between 1 in 12,000 and 1 in 15,000 live births. The distinction of chromosome by parental origin is due to imprinting and PWS has the sister syndrome Angelman syndrome that affects maternally imprinted genes in the region.

PWS is characterized by hyperphagia and food preoccupations, as well as small stature and learning difficulties.

Traditionally, PWS was diagnosed by clinical presentation. Currently, the syndrome is diagnosed through genetic testing, and is recommended for newborns with pronounced hypotonia. Early diagnosis of PWS allows for early intervention as well as the early prescription of growth hormone. Daily recombinant growth hormone (GH) injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.

Diagnosis/testing

PWS should be considered when presented with a hypotonic (floppy) newborn. Accurate consensus clinical diagnostic criteria exist, but the mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternally contributed Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13. Such testing detects over 97% of patients.

Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who are too young to manifest sufficient features to make the diagnosis on clinical grounds or in those individuals who have atypical findings.

PWS phenotype

The classic PWS presentation includes:

• short stature
• small hands and feet
• hypotonia and poor muscle development
• excess fat, especially in the central portion of the body
• narrow forehead
• almond shaped eyes with thin, down-turned lips
• light skin and hair relative to other family members
• lack of complete sexual development in adolescence

Genetics

PWS is caused by absence of the paternally derived PWS/AS region of chromosome 15 (15q11-13) by one of several genetic mechanisms, including uniparental disomy, imprinting mutations (i.e. inappropriate "paternal imprinting"), chromosome translocations, and gene deletions. The genes responsible for Prader-Willi syndrome are expressed only on the paternal chromosome. (Interestingly, a deletion on the maternal chromosome causes Angelman syndrome.) This is the first known instance of imprinting in humans, and is a fascinating model of this genetic phenomenon.

The risk to the sibling of an affected child of having PWS depends upon the genetic mechanism which caused the disorder. The risk to siblings is <1% if the affected child has a gene deletion or uniparental disomy, up to 50% if the affected child has a mutation of the imprinting control center, and up to 25% if a parental chromosomal translocation is present. Prenatal testing is possible for any of the known genetic mechanisms.

Traits of PWS

Sleep disorders are common. These can result in sleepiness and increased difficulties with mood and behavior.

Neuro-cognitive

Individuals with PWS are at risk for learning and attention difficulties. Mild to moderate intellectual disability is common. Sensory integration difficulties can cause stress.

Behavioral

Prader-Willi Syndrome comes with insatiable hunger. People with PWS constantly feel like they are starving. They may go to extreme lengths to find food, such as eating food scraps from the garbage, stealing food, or eating frozen or pet food.

Mood issues are common and can lead to behavior issues. People with PWS can struggle with irritability, anxiety, and stubbornness. They may experience emotional outbursts, especially when denied food. Coping with changes in routine can be difficult for them. They may develop obsessive-compulsive behaviors and skin picking. Experts advise caregivers to create structure and routine, be consistent, offer frequent praise, and empathize with the person's feelings.

Endocrine

There are several aspects of PWS that support the concept of growth hormone deficiency in individuals with PWS. Specifically, individuals with PWS have short stature, are obese with abnormal body composition, have reduced fat free mass (FFM), have reduced LBM and total energy expenditure, and have decreased bone density.

PWS is characterized by hypogonadism. This is manifested as undescended testes in males and benign premature adrenarche in females. Testes may descend with time or can be managed with surgery or testosterone replacement. Adrenarche may be treated with hormone replacement therapy.

Treatment

Prader-Willi Syndrome has no "cure", however, several treatments are in place to lessen the symptoms of the condition. During infancy, subjects should undergo therapies to improve muscle tone. During the school years, children benefit from a highly structured learning environment as well as extra help.

Food should be kept under lock and key to prevent overeating. Health complications from overeating and obesity are a significant risk.

Researchers are investigating the drug pitolisant for PWS. Various clinical trials test different options.

Carer pages: Prader-Willi syndrome

See also

• Intellectual disability
• Genetic counseling: Prader-Willi Syndrome - Prenatal
• Excoriation disorder
• Sensory processing disorder
• Challenging behavior

Additional material - Papers

• Google Scholar

External links

• AAFP Overview A clear and concise overview of PWS.
• Prader-Willi Syndrome Associations:
  • International PWS Organization
  • PWSA-NZ
  • PWSA-UK
  • PWSA-USA
  • PWSA-USA State Chapters
  • PWSA-ZA
  • AMSPW (Madrid, Spain)
• PWS Notes A wiki covering PWS for parents
• Foundation for Prader Willi Research
• Gretton Homes - UK Care homes supporting people with PWS