Prader-Willi Syndrome



Prader-Willi syndrome (PWS) is a genetic syndrome characterized by the following:

  • Severe hypotonia and poor feeding in early infancy followed by hyperphagia and obesity (unless eating is strictly controlled) in later infancy or early childhood
  • Global developmental delay and/or intellectual disability
  • Behavioral problems (obsessive-compulsive behavior, temper tantrums)
  • Hypogonadism


1/5,000 to 1/30,000 live births


  • 1/8,000 to 1/52,000 worldwide
  • United States: 1/16,000 to 1/25,000
  • Males = females

Imprinted genes are those whose expression is determined by the parent who contributed them. For most genes, two working copies are inherited—one from each parent. However, with imprinted genes, only one working copy is inherited. Depending on the gene, either the copy from the mother or the copy from the father is epigenetically silenced through methylation (the addition of methyl groups during egg/sperm formation). PWS arises due to the loss of the critical region (SNORD 116-1 snoRNA cluster) on the paternal copy of 15q11.2-13, by either deletion or methylation. Loss of the maternal copy of 15q11.2-13 causes Angelman syndrome.

  • In PWS
    • Paternal deletion (65–75% of those affected)
      • Risk of recurrence is <1%.
    • Maternal uniparental disomy (UPD) (20–30% of those affected)
      • Risk of recurrence is <1%.
    • Imprinting center defect (1–3% of those affected)
      • Epimutations without deletion—risk of recurrence is <1%
      • Deletion: Risk of recurrence is up to 50%.

Risk Factors

None known

Commonly Associated Conditions

  • Growth hormone deficiency (primary, not a consequence of obesity)
  • Strabismus (60–70%)
  • Scoliosis (40–80%)
  • Recurrent respiratory infections (50%)
  • Epilepsy (up to 25%): usually focal
  • Hypothyroidism (15%)
  • Adrenal insufficiency
  • Obesity-related conditions (type 2 diabetes mellitus [DM], sleep apnea, atherosclerosis, cor pulmonale)
  • Variety of psychiatric states, including autistic-like behaviors (19%)
  • Rectal gouging
  • Osteoporosis
  • Premature adrenarche, delayed menarche/testicular decent
  • Reduced lean mass and increased fat mass (when compared to obese controls)
  • Decreased ability to vomit
  • Increased tolerance of pain
  • Sterility

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