Prader-Willi Syndrome Clinical Presentation

Updated: Aug 27, 2021
  • Author: Ann Scheimann, MD, MBA; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Infants with Prader-Willi syndrome (PWS) commonly exhibit hypotonia, poor suck (with requirement of gavage feedings), weak cry, and genital hypoplasia (eg, cryptorchidism, scrotal hypoplasia, clitoral hypoplasia). [40] Neonatal hypotonia is one of the hallmark features of this disorder and is a valuable clue to initiate diagnostic testing. [41]

Toddlers with Prader-Willi syndrome demonstrate late acquisition of major motor milestones (eg, sitting at age 12 mo, walking at age 24 mo).

Children aged 1-6 years present with symptoms of hyperphagia with progressive development of obesity.

Short stature is generally present during childhood; a minority of patients present later with lack of pubertal growth spurt. [42]

Sleep disturbances, ranging from central or obstructive sleep apnea to narcolepsy, are common. [43] Exacerbation of obstructive sleep apnea shortly after initiation of growth hormone therapy is a recent concern.

Most patients with Prader-Willi syndrome have growth hormone deficiency, as determined with provocative testing. [42]

Pubic and axillary hair may grow prematurely in children with Prader-Willi syndrome, but other features of puberty are generally delayed or incomplete. [42]

Testicular descent has occurred as late as in adolescence; menarche may occur as late as age 30 years in the presence of significant weight loss. [42]

Mild intellectual disability is common. [44]

Obesity complications (eg, sleep apnea, cor pulmonale, diabetes mellitus, atherosclerosis), hypogonadism (osteoporosis), and behavioral issues are common problems in adults with Prader-Willi syndrome. [45]

Using the vision survey of the Global Prader-Willi Syndrome Registry, Bohonowych et al found the prevalence of strabismus to be 40% in persons with Prader-Willi syndrome, with the prevalence not differing significantly between genetic subtypes. In 91% of cases, the strabismus diagnosis was made before age 5 years, with 42% of individuals with strabismus going on to have surgery for the condition. Along with strabismus, the prevalences of hyperopia and amblyopia (25% and 16%, respectively) were also higher in the study cohort compared with the general population. [46]

Behavioral problems

Patients with Prader-Willi syndrome often demonstrate behavioral problems. [47]  Young children exhibit temper tantrums, stubbornness, and obsessive-compulsive behaviors.

Behavioral issues often compromise the level of academic performance. Obsessive-compulsive behaviors and perseveration are challenging for children with Prader-Willi syndrome in the classroom setting. [44]  Features of psychosis are present in 5-10% of young adults with Prader-Willi syndrome. [48, 49]

Food-seeking behaviors may include eating garbage, eating frozen food, and stealing resources to obtain food. High thresholds for vomiting and pain tolerance can complicate binging on spoiled foods and delay treatment for GI disease. Death due to choking episodes has been reported. [35] After episodes of binge eating (eg, at holidays), both thin and obese individuals with Prader-Willi syndrome have developed abdominal discomfort, with acute gastric dilation observed using radiography. Some patients have developed gastric necrosis. [14]

A study by Gito et al indicated that among persons with Prader-Willi syndrome, food-related behaviors are more severe in males whose condition is deletion related than in females with gene deletion or in males with maternal uniparental disomy. However, these behaviors were found to be milder in males with maternal uniparental disomy than in females with such disomy. [50]

In a small percentage of people with autism spectrum disorder (ASD), changes are found in 15q11.2-q3. Thus, it has been estimated that 25-41% of individuals with Prader-Willi syndrome have ASD, although Dykens et al suggest that these rates are questionable, having been derived from autism screeners given to parents. [51]



Holm et al established the following diagnostic criteria for Prader-Willi syndrome. [52] Based on these guidelines, the diagnosis of Prader-Willi syndrome is highly likely in children younger than 3 years with 5 points (3 from major criteria) or in those older than 3 years with 8 points (4 from major criteria).

  • Major criteria (1 point each)

    • CNS - Infantile central hypotonia

    • GI - Infantile feeding problems and/or failure to thrive

    • Nutrition - Rapid weight gain in children aged 1-6 years

    • Craniofacial - Characteristic facial features such as narrow bifrontal diameter, almond-shaped palpebral fissures, narrow nasal bridge, and down-turned mouth

    • Endocrine - Hypogonadism

    • Developmental - Developmental delay and/or mental retardation

  • Minor criteria (one half point each)

    • Neurologic - Decreased fetal movement and/or infantile lethargy

    • Pulmonary - Sleep disturbance and/or sleep apnea

    • Endocrine - Short stature for predicted height by mid adolescence

    • Dermatologic - Hypopigmentation

    • Orthopedic - Small hands and feet

    • Orthopedic - Narrow hands with straight ulnar border

    • Ophthalmologic – Esotropia and/or myopia

    • Dental - Thick viscous saliva

    • Otolaryngology - Speech articulation defects

    • Psychiatric - Skin picking (Some patients with Prader-Willi syndrome have become anemic from chronic rectal bleeding secondary to skin picking.)

  • Supportive criteria (no points)

    • Neurology - High pain threshold and normal neuromuscular evaluation for hypotonia

    • Gastroenterology - Decreased vomiting

    • Endocrinology - Ineffective thermoregulation, early adrenarche, and/or osteoporosis, adrenal insufficiency [42]

    • Orthopedics – Scoliosis or kyphosis [53]

    • Developmental - Jigsaw puzzle proficiency [52]



See the list below:

  • Prader-Willi syndrome is due to the loss of the paternal copy of chromosome 15q11.2-13. [5]

  • Most cases of Prader-Willi syndrome are sporadic. More than 70% of patients have a deletion of the paternal copy; approximately 25% of patients with Prader-Willi syndrome have maternal uniparental disomy in chromosome 15. The remainder of patients with this disorder have a translocation or other structural alteration in chromosome 15.

  • Most manifestations of Prader-Willi syndrome are attributable to hypothalamic dysfunction.