Identification of a prenatal profile of Cornelia de Lange syndrome (CdLS): A review of 53 CdLS pregnancies

Abstract

Cornelia de Lange Syndrome (CdLS) is a multisystem developmental disorder characterized by growth retardation, cognitive impairment, external and internal structural malformations, and characteristic facial features. Currently, there are no definitive prenatal screening measures that lead to the diagnosis of CdLS. In this study, documented prenatal findings in CdLS syndrome were analyzed towards the development of a prenatal profile predictive of CdLS. We reviewed 53 cases of CdLS (29 previously reported and 24 unreported) in which prenatal observations/findings were available. The review of these cases revealed a pattern of sonographic findings, including obvious associated structural defects, growth restriction, as well as a more subtle, but strikingly characteristic, facial profile, suggestive of a recognizable prenatal ultrasonographic profile for CdLS. In addition the maternal serum marker, PAPP-A, may be reduced and fetal nuchal translucency may be increased in some pregnancies when measured at an appropriate gestational age. In conclusion, CdLS can be prenatally diagnosed or readily ruled out in a family with a known mutation in a CdLS gene. The characteristic ultrasonographic profile may allow for prenatal diagnosis of CdLS in 1) subsequent pregnancies to a couple with a prior child with CdLS in whom a mutation has not been identified or 2) when there are unexplained pregnancy signs of fetal abnormality such as oligo- or polyhydramnios, a low maternal serum PAPP-A level and/or increased nuchal translucency, fetal growth retardation, or structural anomalies consistent with CdLS.

Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally

“…The most common feature reported in patients with CdLS is growth failure, which typically presents in the second trimester . In a review of the prenatal findings in 53 CdLS cases, the average gestational age of IUGR detection was 25 weeks, although it was detected as early as 16 weeks in one case . IUGR typically becomes more significant later in the pregnancy .…”

“…Suggested sonographic criteria for the diagnosis of CdLS include asymmetrical oligodactyly, microcephaly, intrauterine growth restriction (IUGR), and/or diaphragmatic hernia . In addition, a subtle but unique facial profile may also be observed prenatally, including micrognathia with prominent maxilla, prominent skin of the forehead, prominent eyelashes, depression of the nasal root or small nose with anteverted nares, and a long smooth philtrum . Case reports of patients with CdLS identified prenatally with confirmed NIPBL mutations have been described previously, two of which are also part of this study (Cases 1 and 4) .…”

Cornelia de Lange Syndrome: A Variable Disorder of Cohesin Pathology

“…Growth restriction is of prenatal onset, and along with structural findings of limb, diaphragmatic or cardiac anomalies as well as the characteristic facial profile can be helpful diagnostically [17]. Postnatally, there is proportionate small stature with microcephaly, for which specific growth charts have been developed [18], although in milder cases, growth can overlap into the normal range.…”

“…Here we outline guidelines from a number of References [1,16,17,19,[26][27][28][29][30][31][32][33], paying attention to the chronologic age at which complications may arise.…”

Microtia in Cornelia de Lange syndrome: a case from Democratic Republic of the Congo

“…The etiology is genetic, with mutations described in at least five genes, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8 (Ansari et al, 2014). The spectrum of clinical presentations is very broad and ranges from mild to severe intellectual disability, malformations affecting one to multiple systems, and a characteristic facial dysmorphism (Clark et al, 2012). Whereas the morphology of the ear is often a cornerstone for the clinical diagnosis of many syndromes, major anomalies of the external ear are rare in CdLS.…”