126: Prader-Willi syndrome: fetal phenotype can lead to prenatal diagnosis

Abstract

Prader-Willi syndrome (PWS) is a severe neurogenetic disorder characterized by morbid obesity, mental retardation and severe behavioral disorders. PWS can be diagnosed by methylation analysis during invasive prenatal diagnosis procedures, however, prenatal diagnosis is rare. We aimed to characterize PWS fetal phenotype, in order to offer the possibility of prenatal diagnosis. All 99 PWS patients treated at the Israel National Multidisciplinary PWS clinic under the age of 10 years were studied. Clinical features of PWS pregnancies were reported by the mothers. Medical records including ultrasound reports, obstetric records, and genetic results were collected. Results were compared both to normal PWS sibling's pregnancies (n=70) and to the Israeli general population. PWS pregnancies were complicated by higher rates of decreased fetal movements (DFM), small for gestational age (SGA), polyhydramnios, breech presentation and cryptorchidism in males (80.4%, 56.6%, 37.4%, 36.4%, 88% respectively, (Table 1). A combination of 2,3 and 4 features was found in 35,34,15% respectively. In 52% of PWS pregnancies at least 3 features were found and in 87% at least two. High rates of asymmetric fetal growth during the 3rd trimester with increased head to abdominal circumference (HC/AC) ratio were found (38%). When evaluating AC as a marker of asymmetric growth, in 64% of the pregnancies the AC was < 10th% and in 32% < 3rd%. The most common feature accompanying abnormal HC/AC ratio or AC< 5th% was DFM. Doppler studies were mostly normal (84.4%) (Table 2). Amniocentesis was performed in 17 cases (17.2%). Methylation test was not offered and the diagnosis of PWS was missed. We describe distinct prenatal phenotype in PWS. A combination of asymmetric fetal growth with normal Doppler studies and DFM, specifically if accompanied with polyhydramnios/ breech presentation or cryptorchidism. Such phenotype should alert obstetricians to consider the possibility of PWS and perform the diagnostic methylation test when amniocentesis is pursued.View Large Image Figure ViewerDownload Hi-res image Download (PPT)