Early diagnosis is critical for improving prognosis with interventions and treatments. With current medical knowledge and the availability of molecular testing, most cases are diagnosed during early infancy. If screening with the most recent clinical diagnostic criteria (in bold type below) raises a diagnostic suspicion of PWS, this should prompt DNA testing and a methylation analysis test will detect PWS in over 99% of cases. PWS equally affects males, females and all ethnicities. Birth incidence estimates vary – the PWSA(NZ) uses 1 in 16,000 based on mean study data.
Clinical symptoms in infants
- Significant hypotonia, weak cry and poor suck reflex
- Failure to thrive – assisted feeding often required
- Characteristic facial features – almond shape eyes, long and narrow head shape, narrowing at the temples, small down turned mouth with thin upper lip (more likely in those with a deletion.)
- Hypogonadism – genital hypoplasia in males and females, male cryptorchidism
- Reduced fetal movements (other obstetric symptoms may include polyhydramnios, malpresentation – breech, growth restriction or abnormal heart rhythm)
- Excessive sleepiness
- Hypopigmentation – fair colouring compared to family members (more likely in those with a deletion.)
- Small hands and /or feet, narrow hands / straight ulnar borders
- Eye abnormalities – strabismus (esotropia more common than exotropia)
- Thick viscous saliva with crusting at mouth corners
Video by PWS Australia featuring Dr Ohn Nyunt, Paediatric Endocrinologist at Royal North Shore Hospital, Sydney.
Clinical symptoms in children
- Excessive weight gain from 1-2 years
- Global developmental delay
- Sleep disturbance and apnoeas
- Speech and articulation defects
- Eye abnormalities – refractive errors (hyperopia, myopia, astigmatism) and deficiency in stereopsis due to amblyopia or strabismus
- Excessive eating / hyperphagia with central obesity if uncontrolled
- Cognitive impairment
- Hypothalamic hypogonadism, and / or
- Behaviour problems typical of PWS
- Short stature
- Skin picking
Consensus major and minor diagnostic criteria for PWS were developed by Holm et al in 1993. As definitive diagnostic testing was not available in 1993, the criteria were reviewed in 2001 (Gunay-Aygun et al 2001) and some patients with a molecular diagnosis did not meet the 1993 criteria, suggesting they may have been too exclusive.
The revised 2001 recommended diagnostic criteria to prompt DNA testing for PWS can be found here in Table 1.
If clinical findings prompt molecular genetic testing, DNA methylation analysis is recommended. This is the only test that will diagnose PWS caused by all three genetic mechanisms: paternal deletion, maternal uniparental disomy (UPD) 15 and imprinting defect (ID). View this flow chart demonstrating a testing strategy for determining the genetic mechanism in an individual with PWS. (Prader-Willi Syndrome: Driscoll, Miller, Schwartz and Cassidy, revised 2017)