Pediatr Dev Pathol. 2019 Oct;22(5):475-479. doi: 10.1177/1093526619834429. Epub 2019 Mar 19.
Clinical Diagnosis of Classical Cornelia de Lange Syndrome Made From Postmortem Examination of Second Trimester Fetus With Novel NIPBL Pathogenic Variant.
1Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.2Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Classical Cornelia de Lange syndrome (CdLS) is a rare genetic disorder which is associated with distinctive facial features, growth retardation, significant intellectual disability and global developmental delay, hirsutism, and upper-limb reduction defects. Classical CdLS is associated with pathogenic variants in NIPBL. We present a clinical diagnosis of classical CdLS made in a second trimester male fetus with advanced maceration who had undergone intrauterine death at 15 + 6 weeks gestation. The diagnosis was suspected after multiple congenital anomalies were identified on fetal postmortem examination. These included intrauterine growth retardation, upper limb anomalies, ventricular septal defect and diaphragmatic hernia, and skeletal and genitourinary abnormalities. Related prenatal screening findings included a raised nuchal translucency and low maternal serum pregnancy-associated plasma protein-A. Targeted molecular sequencing of genes associated with CdLS identified a novel de novo frameshift pathogenic variant in NIPBL, which confirmed the diagnosis. This report describes our case and reviews the current literature on prenatal diagnosis of CdLS. In summary, we demonstrate that clinical diagnosis of CdLS in a second trimester fetus, through postmortem examination findings, is possible, with confirmation through molecular testing.
Cornelia de Lange syndrome; NIPBL; novel pathogenic variant; postmortem; prenatal diagnosis; “horseshoe” adrenal glandPMID: 30890023 DOI: 10.1177/1093526619834429