A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

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Cornelia de Lange Syndrome: A Case Study

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.21.3.7 ◽

2002 ◽

Vol 21 (3) ◽

pp. 7-13 ◽

Cited By ~ 1

Author(s):

Melanie Melanie

Keyword(s):

Growth Retardation ◽

Cornelia De Lange Syndrome ◽

Facial Features ◽

Cognitive Limitations ◽

Limb Reduction ◽

Cornelia De Lange ◽

The Many ◽

Term Management

Cornelia de Lange syndrome (CdLS) is a rare dysmorphogenic disorder characterized by growth retardation, severe cognitive limitations, distinctive facial features, and limb reduction anomalies recognizable at birth. Currently, no single criterion is diagnostic for CdLS, and misdiagnosis is not uncommon. Long-term management of the infant with CdLS requires a coordinated effort among many different specialists. This article presents a general overview of Cornelia de Lange syndrome. It concludes with a case study illustrating the many problems infants with CdLS may have and the great amount of teaching and support that is needed by families affected by CdLS.

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OP06.09: Cornelia de Lange syndrome amenable to early prenatal diagnosis? Lessons from 106 affected fetuses

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.20706 ◽

2019 ◽

Vol 54 (S1) ◽

pp. 104-104

Author(s):

J. Weichert ◽

M.A. Gembicki ◽

D.R. Hartge ◽

C. Eckmann‐Scholz ◽

M. Czugalinski ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Cornelia De Lange Syndrome ◽

Cornelia De Lange

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Deletion of 11q12.3–11q13.1 in a patient with intellectual disability and childhood facial features resembling Cornelia de Lange syndrome

Gene ◽

10.1016/j.gene.2015.07.016 ◽

2015 ◽

Vol 572 (1) ◽

pp. 130-134 ◽

Cited By ~ 6

Author(s):

Martine Isabel Boyle ◽

Cathrine Jespersgaard ◽

Lusine Nazaryan ◽

Kirstine Ravn ◽

Karen Brøndum-Nielsen ◽

...

Keyword(s):

Intellectual Disability ◽

Cornelia De Lange Syndrome ◽

Facial Features ◽

Cornelia De Lange

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A Case of Cornelia de Lange Syndrome: Difficulty in Prenatal Diagnosis

Case Reports in Obstetrics and Gynecology ◽

10.1155/2019/4530491 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3

Author(s):

Tadatsugu Kinjo ◽

Keiko Mekaru ◽

Miyuki Nakada ◽

Hayase Nitta ◽

Hitoshi Masamoto ◽

...

Keyword(s):

Body Weight ◽

Prenatal Diagnosis ◽

Ultrasound Examination ◽

Fetal Mri ◽

Rare Condition ◽

Japanese Woman ◽

Cornelia De Lange Syndrome ◽

Intrauterine Fetal Death ◽

Old Japanese ◽

Cornelia De Lange

We report a case of Cornelia de Lange syndrome (CdLS) where prenatal diagnosis was not made even with major anomaly. A 33-year-old Japanese woman was referred to our institution at 23 weeks of gestation because of fetal forearm defect. Ultrasound examination revealed short forearms and short humeri and femurs (–2.1 SD). The fetal estimated body weight was 450 g (–1.3 SD). Fetal MRI at 26 weeks of gestation revealed short forearms and hypoplasty of hand fingers. Fetal growth restriction became evident thereafter, leading to intrauterine fetal death occurring at 29 weeks of gestation. A stillbirth baby was of 798 g in body weight and 33.0 cm in length. External examination showed a low hairline, synophrys, low-set ear, hypertrichosis, and smooth long philtrum with thin lips. The neck appeared short and broad. Finally, CdLS was diagnosed. The prenatal diagnosis might be possible as the arm findings were totally characteristic in a small fetus, regardless of whether an overhanging upper lip was identified. Because CdLS is a rare condition, it is important to consider its possibility as a part of differential diagnosis.

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P44.17: Second trimester prenatal diagnosis of Cornelia de Lange Syndrome, identification of limb abnormalites with a sinister cause

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.4969 ◽

2007 ◽

Vol 30 (4) ◽

pp. 622-622

Author(s):

T. F. R. Homfray ◽

A. Bhide ◽

I. Jeffery ◽

S. Bower

Keyword(s):

Prenatal Diagnosis ◽

Cornelia De Lange Syndrome ◽

Second Trimester ◽

Cornelia De Lange

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Cornelia de Lange syndrome with borderline IQ: A case presentation

Archives of Clinical Neuropsychology ◽

10.1093/arclin/14.8.678 ◽

1999 ◽

Vol 14 (8) ◽

pp. 678-679

Author(s):

M.G. Navarrete ◽

P.F. Clement

Keyword(s):

Cornelia De Lange Syndrome ◽

Case Presentation ◽

Cornelia De Lange ◽

Borderline Iq

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Three-Dimensional Ultrasound Findings in Cornelia de Lange Syndrome: A Case Report

Case Reports in Obstetrics and Gynecology ◽

10.1155/2012/568351 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Yoichiro Akahori ◽

Hisashi Masuyama ◽

Yumi Masumoto ◽

Yuji Hiramatsu

Keyword(s):

Case Report ◽

Fetal Growth ◽

Three Dimensional ◽

Cornelia De Lange Syndrome ◽

Third Trimester ◽

Nasal Bridge ◽

Arterial Trunk ◽

Ultrasound Findings ◽

Breech Extraction ◽

Cornelia De Lange

Introduction. The objective is to report a case of Cornelia de Lange syndrome (CdLS) diagnosed by detailed observations using three-dimensional sonography.Case Report. A 33-year-old healthy multipara was referred to our hospital at 34-week gestation after severe fetal growth restriction, congenital heart anomaly, and antebrachium abnormality were diagnosed during the third trimester. Further sonography diagnosis on cardiac abnormalities diagnosed the existence of ventricular septal defect in the outflow tract, atrioventricularis communis, and truncus arteriosus communis where the pulmonary artery branched from the common arterial trunk. As for abnormalities of the forearms, ectrodactylia and monodactylism were suspected and the abnormalities were observed sterically by using three-dimensional sonography. A 1986 g (1.07 percentile) male newborn was delivered by assisted breech extraction at 37-week gestation. After birth, from characteristic facies including bushy eyebrow, broad nasal bridge, micrognathia, and abnormalities of the forearms (ectrodactylia and monodactylism), the case was diagnosed with CdLS.Conclusion. Through detailed observation including abnormalities of fingers, we could exemplify this very rare disease as an antenatal diagnoses for fetal growth retardation.

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Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood

Scientific Reports ◽

10.1038/s41598-021-94958-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ana Latorre-Pellicer ◽

Marta Gil-Salvador ◽

Ilaria Parenti ◽

Cristina Lucia-Campos ◽

Laura Trujillano ◽

...

Keyword(s):

Somatic Mosaicism ◽

Purifying Selection ◽

Mosaic Disease ◽

Cornelia De Lange Syndrome ◽

Published Data ◽

Pathogenic Variants ◽

Diagnostic Center ◽

High Prevalence ◽

Strong Source ◽

Cornelia De Lange

AbstractPostzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families.

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A novel USH2A variant in a patient with hearing loss and prenatal diagnosis of a familial fetus: a case report

BMC Medical Genomics ◽

10.1186/s12920-021-01052-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Cong Zhou ◽

Yuanyuan Xiao ◽

Hanbing Xie ◽

Shanling Liu ◽

Jing Wang

Keyword(s):

Hearing Loss ◽

Prenatal Diagnosis ◽

Usher Syndrome ◽

Chinese Patient ◽

Compound Heterozygous ◽

Case Presentation ◽

Pathogenic Variants ◽

Compound Heterozygous Variants ◽

Gene Panels

Abstract Background Usher syndrome (USH) is the most common cause of inherited deaf-blindness. The current study aimed to identify pathogenic variants in a Chinese patient with hearing loss and to report the identification of a novel p.(Phe1583Leufs*10) variant in USH2A, which met the needs of prenatal diagnosis of the patient's mother. Case presentation Genomic DNA obtained from a five-year-old girl with hearing loss was analyzed via the hearing loss-targeted gene panels. We identified the compound heterozygous variants c.8559-2A>G and c.4749delT in Usher syndrome type 2A (USH2A) gene as the underlying cause of the patient; the former variation has been reported in the literature, but not the latter. The parents of the girl were heterozygous carriers. The two variants were classified as pathogenic. Based on these findings, amniotic fluid samples were used for prenatal diagnosis of the couple's fetus, which was found to carry c.4749delT but not c.8559-2A>G variation. During the follow-up period of more than 9 months after the birth of the fetus, it was confirmed that the infant was healthy. Conclusions The results of the present study identified two compound heterozygous USH2A variants in a patient with hearing loss and reported a novel USH2A variant which expands the spectrum of USH2A variants in USH.

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