Prader‐Willi Syndrome

Abstract

Condition Description: Prader-Willi syndrome (PWS) is caused by abnormal expression of genes on chromosome 15 due to abnormal imprinting. 1 This is most commonly due to a deletion of the paternallyderived chromosome 15q11-q13, but can also be due to uniparental disomy 1 (UPD) or a mutation involving the imprinting center on chromosome 15 2 . Recommended testing strategy is presented as an algorithm at the end of the sheet 3 . Diagnostic Criteria:1. Severe Hypotonia 2. Feeding problems until age 2 at which time insatiable appetite develops leading to increased obesity risk 3. Short stature with small hands and feet 4. Hypogonadism (small penis, undescended testes) 5. Characteristic behaviors (obsessive, temper tantrums, skin picking) 6. Global developmental delay, mild to moderate cognitive impairment 7. Hypopigmentation compared to family background Other associated findings: Growth Hormone deficiency, hypogonadotropic hypogonadism, risk for insulin resistance and diabetes, sleep apnea (obstructive and central), high pain threshold Differential diagnosis 3 : Infantile Hypotonia: Spinal Muscular Atrophy, Congenital Myotonic Dystrophy or other myopathy/neuropathy, other chromosomal abnormality. Older children (obesity/cognitive impairment): Fragile X, Bardet Biedl syndrome, chromosomal abnormality Action required: Follow diagnostic algorithm to confirm diagnosis. Consider referral for clinical genetics evaluation (link to clinics) and endocrinology. Follow management recommendations. 2,3

Prader-Willi syndrome

“…Several other approaches to management have been published recently. 4,34,[145][146][147][148] infancy Special nipples or gavage feeding is usually needed to ensure adequate nutrition, as poor suck will result in failure to thrive if untreated. Growth measurements (height, weight, and head circumference) should be obtained and plotted at diagnosis and thereafter on a regular and frequent basis, at least every 2-3 months for the first year of life and as long as obtaining adequate calories is an issue.…”

The expression and assessment of emotions and internal states in individuals with severe or profound intellectual disabilities

“…The physical phenotype includes distinctive facial features, hypotonia at birth, hypogonadism, small hands and feet and small stature (e.g. Cassidy & Driscoll, 2009). After an initial poor suckling relax, hyperphagia onsets in infants between the age of 1 and 6 years (Cassidy, 1997).…”

Circulating adiponectin levels, body composition and obesity-related variables in Prader–Willi syndrome: comparison with obese subjects

“…1 It is a congenital disorder characterized by short stature, muscular hypotonia, hypogonadism, mild mental retardation, diminished growth hormone secretion, hyperphagia and obesity which is extremely severe in some cases. [1][2][3] Approximately 70% of PWS cases are due to a paternal deletion on chromosome 15 (15q11-q13 region), 25% of PWS cases have maternal uniparental disomy (UPD) of chromosome 15 and the remaining cases result from genetic imprinting defects. [4][5][6][7][8] Much interest now revolves around the role of adipose tissue as an endocrine organ, capable of producing hormones and cytokines such as tumor necrosis factor-a, plasminogen activating inhibitor-1, leptin, interleukin-6, resistin and, more recently, adiponectin.…”