952 Prenatal phenotype of 47,XXY (Klinefelter syndrome)

Abstract

The phenotypic description of prenatal Klinefelter syndrome (KS), or 47,XXY, is currently limited to case reports. There is a gap in knowledge regarding prenatal presentation of KS. We hypothesize that a significant percentage of pregnancies complicated by fetal KS will have associated ultrasonographic findings. We retrospectively identified all fetuses with cytogenetically confirmed 47,XXY in the prenatal period or up to age 5 years, with prenatal records available for review from four prenatal diagnostic referral centers between 2006 and 2019. Ultrasound reports were reviewed to assess for the presence of increased nuchal translucency (NT) and abnormalities at the second trimester anatomy ultrasound. Additionally, we reviewed results of cell free DNA and serum analyte testing to inform our understanding of prenatal screening tests in the setting of fetal KS. A total of 42 subjects with confirmed cytogenetic diagnosis of 47,XXY and prenatal records available for review were identified: 38 had a prenatal diagnosis of KS and 4 had a postnatal diagnosis. One case was excluded as cytogenetic analysis demonstrated mosaic KS, leaving a cohort of 41 subjects. NT was increased ≥3.0mm in 6 of 26 (23.1%) of cases that had a documented measurement. A second trimester anatomical survey was available for review in 24/41 affected pregnancies. In 7 of 24 (29.2%) ultrasounds, a fetal abnormality was identified. These include 3 brain anomalies, 1 cardiac abnormality, 1 echogenic bowel, and 2 limb abnormalities (table). In subjects who had cell free DNA performed, 92.6% had a positive result for 47,XXY (25/27); in subjects who had serum analytes performed, 36.3% (4/11) had a positive result. This case series expands our knowledge of the prenatal presentation of KS by identifying 1st and 2nd trimester fetal sonographic abnormalities as well as serum analyte abnormalities.View Large Image Figure ViewerDownload Hi-res image Download (PPT)