Analysis of clinical and genetic characteristics in 10 Chinese individuals with Cornelia de Lange syndrome and literature review

PurposeCornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder, and cases caused by variants in SMC3 are infrequent. This article describes a case of CdLS related to a pathogenic variant in SMC3 and performs a literature review.MethodsWe collected clinical data and biological samples from a 12-year-old boy with “short stature for 11 years”. Gene variants in the proband were detected by whole-exome sequencing, and the variants in his parents were verified by Sanger sequencing. All SMC3-related CdLS patients from the PubMed and Web of Science databases were collected and summarized using the available data.ResultsA pathogenic variant in SMC3 in the proband, c.1942A>G, was identified. Neither of his parents carried the same variant. Twenty-eight patients were diagnosed with CdLS with variants in SMC3, including the cases in this study and those reported in the literature, where half of the variant types were missense, followed by 32% (9/28) with a deletion and 11% (3/28) with a duplication. All patients showed symptoms of verbal development delay and intellectual disability to different degrees, and 90% patients had long eyelashes while 89% patients had arched eyebrows.ConclusionThis study summarized different gene variants in SMC3 and the frequencies of the various clinical manifestations according to the reported literature. For CdLS caused by SMC3 variants, short stature and facial dysmorphic features are the two most important clinical clues. Definite diagnosis of this rare disease may be challenging clinically; thus, it is significant to use molecular diagnosis.

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Dermatological manifestations of the Cornelia de Lange syndrome

Archives of Dermatology ◽

10.1001/archderm.94.1.38 ◽

1966 ◽

Vol 94 (1) ◽

pp. 38-43 ◽

Cited By ~ 4

Author(s):

F. N. Salazar

Keyword(s):

Cornelia De Lange Syndrome ◽

Cornelia De Lange

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Faculty Opinions recommendation of Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1027601.334640 ◽

2005 ◽

Author(s):

Conly Rieder

Keyword(s):

Sister Chromatid ◽

Cornelia De Lange Syndrome ◽

Sister Chromatid Separation ◽

Cornelia De Lange

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i-gel: a new supraglottic device for effective resuscitation of a very low birthweight infant with Cornelia de Lange syndrome

BMJ Case Reports ◽

10.1136/bcr-2014-209124 ◽

2015 ◽

Vol 2015 (mar24 2) ◽

pp. bcr2014209124-bcr2014209124 ◽

Cited By ~ 3

Author(s):

A. Galderisi ◽

G. De Bernardo ◽

E. Lorenzon ◽

D. Trevisanuto

Keyword(s):

Low Birthweight ◽

Cornelia De Lange Syndrome ◽

Very Low Birthweight ◽

Cornelia De Lange ◽

Very Low Birthweight Infant

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

Diagnostics ◽

10.3390/diagnostics11010142 ◽

2021 ◽

Vol 11 (1) ◽

pp. 142

Author(s):

Anca Maria Panaitescu ◽

Simona Duta ◽

Nicolae Gica ◽

Radu Botezatu ◽

Florina Nedelea ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Cornelia De Lange Syndrome ◽

Facial Features ◽

Genetic Condition ◽

Case Presentation ◽

Pathogenic Variants ◽

Limb Reduction ◽

Ultrasound Findings ◽

Prenatal Management ◽

Cornelia De Lange

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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Targeted Gene Sequencing, Bone Health, and Body Composition in Cornelia de Lange Syndrome

Applied Sciences ◽

10.3390/app11020710 ◽

2021 ◽

Vol 11 (2) ◽

pp. 710

Author(s):

Ángel Matute-Llorente ◽

Ángela Ascaso ◽

Ana Latorre-Pellicer ◽

Beatriz Puisac ◽

Laura Trujillano ◽

...

Keyword(s):

Body Composition ◽

Lean Mass ◽

Bone Health ◽

Cornelia De Lange Syndrome ◽

Areal Bone Mineral Density ◽

Childhood And Adolescence ◽

Mineral Density ◽

Calcium Phosphorus ◽

Cornelia De Lange ◽

Targeted Gene Sequencing

The aim of this study was to evaluate bone health and body composition by dual-energy X-ray absorptiometry (DXA) in individuals with Cornelia de Lange Syndrome (CdLS). Overall, nine individuals with CdLS (five females, all Caucasian, aged 5–38 years) were assessed. Total body less head (TBLH) and lumbar spine (LS) scans were performed, and bone serum biomarkers were determined. Molecular analyses were carried out and clinical scores and skeletal features were assessed. Based on deep sequencing of a custom target gene panel, it was discovered that eight of the nine CdLS patients had potentially causative genetic variants in NIPBL. Fat and lean mass indices (FMI and LMI) were 3.4–11.1 and 8.4–17.0 kg/m2, respectively. For TBLH areal bone mineral density (aBMD), after adjusting for height for age Z-score of children and adolescents, two individuals (an adolescent and an adult) had low BMD (aBMD Z-scores less than –2.0 SD). Calcium, phosphorus, 25-OH-vitamin D, parathyroid hormone, and alkaline phosphatase levels were 2.08–2.49 nmol/L, 2.10–3.75 nmol/L, 39.94–78.37 nmol/L, 23.4–80.3 pg/mL, and 43–203 IU/L, respectively. Individuals with CdLS might have normal adiposity and low levels of lean mass measured with DXA. Bone health in this population seems to be less of a concern during childhood and adolescence. However, they might be at risk for impaired bone health due to low aBMD in adulthood.

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