Approach

Prader-Willi syndrome (PWS) is a rare (present in approximately 1 in 10,000 to 1 in 25,000 live births) multisystem neurological disorder and is caused by paternally inherited genetic defects on chromosome 15q11-q13 due to any of three genotypes: deletion, maternal uniparental disomy of chromosome 15, or imprinting defect.[1][2][3]​​​[26]

It is usually diagnosed in infants and young children by identification of characteristic features with confirmation using genetic testing.[1][2][3]​​​[26]​ The clinical features of PWS may be extensive and wide ranging; in general, however, genetic testing in an infant or young child should be prompted by the presence of hypotonia, difficulty feeding, and/or hypogonadism.[2]

Complications of PWS include type 2 diabetes and gastrointestinal and respiratory issues.[2][3]​​ See Complications.

History

Consider PWS in an infant or young child with:[1][2][3]​​​

  • Features of hypotonia (e.g., weak cry, poor suck, gross motor delay)

  • Difficulty feeding

    • In practice, if a baby has not required a feeding tube or assisted feeding in the neonatal period it is very unlikely that they have PWS.

Prenatally, there may be a history of polyhydramnios and decreased fetal movements.[2][26]

Although PWS is usually diagnosed in infants and young children, patients may also present in adolescence or early adulthood.[1][2][3]​​​ Depending on the age of the patient, other features from the history include:[1][2][3]​​​

  • Weight gain (which usually begins around 18 to 26 months of age) and hyperphagia (which usually begins around 6 to 12 years of age)[26]

  • Developmental delay

  • Cognitive disability

  • Sleep abnormalities

  • Characteristic behaviours (e.g., temper tantrums, skin picking, other compulsive and autistic spectrum behaviours)[1][26]

  • Psychiatric disorders (e.g., psychosis, mood disorders).[26]

Less common features include:[1][2][3]​​​

  • Seizures

  • Premature adrenarche.

The diagnosis is unlikely in patients with obesity who do not have a history of neonatal feeding problems, hypotonia, or developmental delay.[17]

[Figure caption and citation for the preceding image starts]: If a baby has not required a feeding tube or assisted feeding in the neonatal period it is very unlikely that they have PWSCourtesy of Dr Jennifer Miller [Citation ends].com.bmj.content.model.Caption@633e440f

Physical examination

Examine the patient for the key physical features of PWS:[1][2][3]​​

  • Central hypotonia, which is common in infants and tends to improve with age but is present throughout life[26]

  • Hypogonadism[26]

    • Other endocrine disorders such as growth hormone deficiency, diabetes mellitus, and hypothyroidism may also be present.

Other physical features include:

  • Short stature[1][2][3]​​[26]

  • Small hands and feet[1][2][3]​​

  • Hypopigmentation[2]

  • Ocular problems (e.g., strabismus, myopia)[1][2][3]​​

  • Spinal deformities[1][2][3]​​

  • Developmental dysplasia of the hip in neonates (although this is uncommon).[1][3]​​

Initial investigations

Genetic testing

Organise DNA methylation testing if PWS is suspected, which will confirm the diagnosis in >99% of patients with PWS.[1][3]​​ In general, key features that should prompt DNA methylation testing include one or more of the following: hypotonia, difficulty feeding, and/or hypogonadism.[2] A full list of clinical features by age that can help guide which patients should undergo DNA methylation testing has been proposed. See Criteria.

Refer the patient to a medical geneticist for further genetic testing if PWS is confirmed to determine the specific genotype (deletion, maternal uniparental disomy of chromosome 15, or imprinting defect).[3][25]

Use of this content is subject to our disclaimer