Cornelia de Lange syndrome: To diagnose or not to diagnose in utero?

Abstract

Cornelia de Lange syndrome (CdLS) is an inherited condition with a wide spectrum of phenotypic anomalies, consisting mainly of growth impairment, multi‐organ abnormalities, and neurocognitive delay. Clinical diagnostic criteria after birth are well defined, whereas when to suspect the syndrome during intrauterine life still remains undefined. This review summarizes the main possible prenatal findings in CdLS, suggesting that a skilled ultrasound scan in cases of intrauterine growth restriction associated with other fetal abnormalities may improve the chance of prenatal diagnosis of CdLS, especially in families known to be at high risk. We propose that, following a sequence of detailed scans and examinations, CdLS affected fetuses could be diagnosed in utero, when one or more conditions (among them, intrauterine growth restriction, limb defects, facial abnormalities, diaphragmatic hernia, and heart diseases) are detected, and possibly confirmed by specific molecular testing. Birth Defects Research 109:771–777, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

Fetal cardiac abnormalities: Genetic etiologies to be considered

“…Common CHD findings include ventricular septal defect and atrial septal defect, truncus arteriosus communis, TOF, mild cardiac hypertrophy, atrial ventricular septal defect, stenosis or coarctation of aorta, and single ventricle …”

“…Although prenatal diagnosis has been achieved in a number of cases, it still remains a challenge . Asymmetrical forearm anomalies with oligodactyly along with elevated NT, microcephaly, and/or IUGR should prompt the search for this diagnosis .…”

“…Prenatally, a characteristic facial profile has been reported: frontal bossing, micrognathia, depressed nasal root, prominent hyperconvex featureless philtrum, thin lips, and low set ears. Even the unusually long hair, synophrys with arched eyebrows, forehead hirsutism, and long eyelashes have been observed by ultrasound …”

“…In the first trimester, increased NT and low PAPP‐A have been reported; however, normal values for NT and PAPP‐A levels have also been found in fetuses with established diagnosis of CdLS …”

“…The exact recurrence risk for unaffected parents is classically quoted as 1.5% because of germline mosaicism. Recently higher figures (up to 5%) have been proposed and the exact recurrence is still unknown (Table ) …”