History and exam

Key diagnostic factors

common

central hypotonia

Present in 88% of infants, and associated with poor suck, weak cry, and gross motor delay.[2][3]​​​ Tends to improve with age but is present throughout life.[1][2]​​[24]

poor suck

Common in neonates.[1][2][3]​​​ A feature of hypotonia.

weak cry

Common in neonates.[2][3]​​ A feature of hypotonia.

feeding difficulties

Present in almost all neonates.[1][2][3]​​​ 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 Prader-Willi syndrome.

hypogonadism

Present in 90% to 100% of patients in infancy. Seen in both sexes.[1][2][3]​​​ Manifests as genital hypoplasia, pubertal delay, and infertility in the vast majority of patients.[1][3]​​ In practice, hypogonadism can only be diagnosed in infancy and adolescence.

weight gain and hyperphagia

Occurs in 90% to 100% of patients. At approximately 2 years of age patients start gaining weight without a change in calories, followed (at around 5 years of age) by increased interest and awareness of food, and then hyperphagia (at around 9 years of age).[25][27]​​​​ Leads to obesity if access to food is not limited.[1][2][3]​​​[28]

Other diagnostic factors

common

developmental delay

Delays in speech, motor, and language development are present in 90% to 100% of patients, although language delays can be variable.[25]​ Social interaction skills may also be delayed.[3]

cognitive disability

Present in 90% to 100% of patients, but variable.[25] Most patients have mild disability, but some may have severe cognitive or learning disabilities.[1][2][3]​​​ 

endocrine disorders

As well as hypogonadism, endocrine disorders that may be present include growth hormone deficiency, diabetes mellitus, and hypothyroidism.[1][2][3]​​​[26]​​

Central adrenal insufficiency is rare and can be seen in up to 10% of patients.[29]​ It is not routinely screened for in patients with Prader-Willi syndrome.[30]​​ 

sleep abnormalities

Present in 30% to 40% of patients.[25][31]​​​ Includes central or obstructive sleep apnoea and sleep/wake disturbances (excessive daytime sleepiness and difficulty sustaining sleep at night).[1][2][3]​​​ Narcolepsy and cataplexy are present at higher rates in patients with Prader-Willi syndrome compared with the general population.​[1][2][3]​​​[25]​​[32]

behavioural abnormalities

Characteristic behavioural abnormalities typically emerge during childhood.[3] These commonly include temper tantrums, skin picking or other compulsive behaviours, and autistic-spectrum behaviours (present in 70% to 90% of patients) which include need for schedule, restrictive or repetitive behaviours, and repetitive questioning.[1][2][3]​​​[33]​​​ 

psychiatric disorders

Psychosis tends to occur in adulthood, especially in those with the maternal uniparental disomy of chromosome 15 type of Prader-Willi syndrome.[34] However, psychosis may also occur in childhood and adolescence.[3] Mood disorders may be present from childhood onwards.[1][2][3]​​​ 

short stature

Present in 60% to 70% of patients, but improves with growth hormone therapy.[2][25]​​ Children may have poor linear growth.[2][3]​​

small hands and feet

Present in 70% to 90% of patients, but can improve with growth hormone therapy.[2][25]

hypopigmentation

Primarily seen in patients of all ages with deletion 15q type of Prader-Willi syndrome.[2] Uncommon in those with maternal uniparental disomy 15 or imprinting defect types of Prader-Willi syndrome.[2][25]

ocular problems

Includes strabismus and myopia.[1][2][3]​​​​​​ Present in 40% to 60% of patients.[2][25][35]​​​​ Usually diagnosed before 5 years of age.[2][25][36]​​​​

spinal deformities

Includes scoliosis, kyphosis, and kyphoscoliosis.[1][2][3]​​​ Present in 40% to 80% of patients.[35] Scoliosis may occur at any age, but there is a bimodal peak in infancy and during adolescence.[2][3]

polyhydramnios

A common feature prenatally.[2][3][26]​

decreased fetal movements

A common feature prenatally.[2][3][26]​

uncommon

developmental dysplasia of the hip

Present in 10% of infants.[3] Diagnosis is made using ultrasound or x-ray of the hip.[1][3]​​ In practice, x-ray is used in infants, and ultrasound is used for patients aged 3-12 months.[37]​

seizures

Present in 10% to 20% of all patients.[38]​ Typically generalised and easy to control.

premature adrenarche

​Premature adrenarche is the appearance of pubic or axillary hair before 8 to 9 years of age.[3] It is present in 15% to 30% of patients and is associated with elevated DHEA-S (dehydroepiandrosterone sulfate) levels and advanced bone age.[39]​ 

Risk factors

weak

older maternal age (>35 years)

Associated with PWS due to maternal uniparental disomy of chromosome 15 as a result of meiosis (non-disjunction) errors and trisomy rescue occurring in early pregnancy.[24]

hydrocarbon exposure

Incidence of PWS may be increased in children of males with occupations associated with hydrocarbon exposure.[17]

conception using assisted reproductive technology

May be associated with PWS due to interference with the methylation DNA pattern required to control normal gene activity.[17]

sibling with Prader-Willi syndrome (PWS)

Associated with increased risk of PWS, but level of risk is dependent on the genotype.[25]​ Risk of PWS can be up to 50% if the affected sibling has an imprinting defect, up to 25% if a parental chromosome translation is present, and less than 1% if there is deletion or uniparental disomy.[25]

Use of this content is subject to our disclaimer