Neonatal hypotonia (low muscle tone), reduced fetal movement, feeding difficulties, and cryptorchidism (undescended testes) should immediately suggest a diagnosis of Prader-Willi syndrome (PWS), according to a recent study.
Early diagnosis of PWS is critical, as it allows timely therapeutic intervention such as growth hormone (GH) administration to improve growth and motor development; physiotherapy, speech therapy, and nutritional guidance to help with feeding difficulties and prevention of early-onset obesity.
One problem clinicians face when trying to diagnose PWS is that some signs of the disease, such as abnormally low levels of muscle tone (hypotonia) and inability to suck (requiring tube feeding), can transiently affect otherwise healthy preterm infants, or be a sign of other serious conditions, including sepsis, neurological disease, and metabolic disorders.
To gain a better understanding of key perinatal features of PWS, researchers analyzed case records of 90 patients (54 male, 36 female) seen at a multi-disciplinary clinic in the Royal Hospital for Children in Glasgow, Scotland, between 1991 and 2015, and a birth questionnaire completed by parents.
As key features of PWS in newborns, the team identified cryptorchidism (in 94% of males), preterm birth (26%), birthweight less than 2,500 grams (24%), excessive amniotic fluid volume during pregnancy (polyhydramnios, 23%), breech presentation (23%), and the need for nasogastric feeding (83%).
Furthermore, reduced fetal movement was reported in 82.5% of the patients, compared with 4% in healthy siblings.
The investigators also found that of 35 children born since 1999, 23 were clinically diagnosed with PWS within 28 days, while the diagnosis was delayed beyond day 28 in 12 infants — between months 1 and 12 in seven children, and between 3.75 and 10.5 years of age in five children.
The diagnoses in these 12 children were delayed despite the presence of typical PWS features, including hypotonia (100%), cryptorchidism (83% males), feeding difficulties (75%), and reduced fetal movement (66%). Causes other than PWS, such as neuromuscular disease, were considered in nine of these patients.
Overall, the team suggested that “neonatal hypotonia, reduced [fetal movement], feeding difficulties, and cryptorchidism should immediately suggest PWS” in newborns. Awareness of these typical PWS features in newborns “is required to allow prompt detection even in the presence of confounding factors such as prematurity,” the team said.
Researchers also emphasized that “although features such as preterm birth, low birthweight, small for gestational age, operative delivery, and malpresentation are not specific to PWS, their combined presence in the context of hypotonia and feeding difficulties should evoke PWS.”
Of note, a delayed diagnosis of PWS can generate distress and anxiety among parents. The team highlights the case of a mother involved in the study. She stated that “as the hospital didn’t know what was wrong, we were not allowed to go home until our daughter could take the bottle.
“On finding out about her condition we realized that she ticked all the boxes [for a PWS diagnosis] and we feel that the hospital should have recognized the condition. Instead we were told she had cerebral palsy.”
The child was diagnosed with PWS at 9 months.