Prader-Willi syndrome (PWS) should be considered in the differential diagnosis of infants with limited womb mobility, polyhydramnios — excessive accumulation of amniotic fluid — low birth weight and muscle tone, feeding difficulties, and also among those born by caesarean section, a study says.
Considering PWS in the diagnostic process could lead to earlier identification of the complex genetic condition, which could in turn prompt earlier treatment, the researchers said.
The study, “Perinatal features of Prader-Willi syndrome: a Chinese cohort of 134 patients,” was published in the Orphanet Journal of Rare Diseases.
PWS is characterized by severe loss of muscle tone, called hypotonia, and by feeding problems in early infancy. The disease is caused by genetic alterations that lead to the loss of function of genes inherited from the father and located on chromosome 15. Collectively, these genes control metabolism, appetite, growth, intellectual function, and social behavior.
“Genetic diagnosis for PWS is now easily available, in which diagnosis can be made in most patients within the first months of life even in prenatal period if obstetricians or neonatologists can recognize the perinatal features of PWS well,” the researchers said. Perinatal refers to the time period from 22 weeks gestation to seven days after birth. Neonatal refers solely to the time period after birth, extending three weeks beyond the perinatal period.
“Recognizing perinatal features of PWS will be helpful for early diagnosis and multidisciplinary care of affected infants,” the investigators said.
In this study, researchers from the Zhejiang University School of Medicine, in China, and their colleagues sought to document the perinatal features associated with PWS. The team compared anonymous clinical data from 134 Chinese patients with Prader-Willi syndrome with that of individuals from the general population and from other previously reported large groups of patients from France, the U.K. and the U.S.
The patient data in China was obtained from a Chinese PWS Registry and included participants’ perinatal and neonatal characteristics and genetic information.
The analysis showed that 115 patients (85.8%) carried a mutation that removed a portion of the paternal DNA on chromosome 15, called a 15q11-q13 deletion. In addition, 19 (14.2%) had maternal uniparental disomy (UPD). In PWS, maternal UPD occurs when a child receives two copies of chromosome 15 from the mother and none from the father, resulting in the complete loss of the paternal genes.
All children included in the study were born between October 1997 and August 2018, and more than half (54.5%) were boys. Age at diagnosis ranged from 10 days to 17 years.
Analyses showed that patients with PWS were born from older mothers (30.5 years), compared with individuals from the general population (26.7 years). This was especially true among those with UPD, whose mothers were even older (36.0 years).
The registry data also revealed that most mothers of patients with PWS (87.9%) reported a decrease in fetal movements during pregnancy. In addition, 42.5% of the PWS mothers had polyhydramnios, with too much amniotic fluid during preganancy, while 18.7% had oligohydramnios, which is less amniotic fluid than normal.
Most infants with PWS (82.8%) were born by cesarean section. At birth, approximately a third of the infants (32.1%) had breathing problems and almost all babies showed signs of low muscle tone (98.5%), had a weak cry or were not able to cry at all (97.8%).
Almost all infants with PWS had difficulties feeding (99.3%) and most of them had failure to thrive (94.8%). Most infants required a feeding tube while in the hospital (69.4%), but the majority no longer used it after being discharged (97.8%).
The rates of premature births (16.4% versus 7.2%) and low birth weight (34.3% versus 7.1%) also were higher among those with PWS compared with the general population.
“Our study is helpful to better understand the perinatal features of PWS in China, which will benefit for early diagnosis and treatment,” the investigators said.
“Differential diagnosis of PWS should be highlighted” in pre- and post-natal care, they said.
“Moreover, our results provide valid evidence for further research and promote PWS screening into the newborn screening program in China,” the team concluded.