Incidence and clinical features of X-linked Cornelia de Lange syndrome due toSMC1L1 mutations

AbstractCornelia de Lange Syndrome (CdLS) is a rare genetic disorder, which causes a range of physical, cognitive, and medical challenges. To retrospectively analyze the clinical characteristics and genetic variations of Chinese patients, and to provide experience for further diagnosis and treatment of CdLS in Chinese children, we identified 15 unrelated Chinese children who presented with unusual facial features, short stature, developmental delay, limb abnormalities, and a wide range of health conditions. In this study, targeted-next generation sequencing was used to screen for causal variants and the clinically relevant variants were subsequently verified using Sanger sequencing. DNA sequencing identified 15 genetic variations, including 11 NIPBL gene variants, two SMC1A gene variants, one RAD21 gene variant, and one HDAC8 variant. The phenotype of these patients was summarized and differences between this cohort and another four groups were compared. The clinical manifestations of the patients in this cohort were mostly consistent with other ethnicities, but several clinical features in our cohort had different frequencies compared with other groups. We identified 15 deleterious variants of which 11 were novel. Variants in the NIPBL gene were the most common cause in our cohort. Our study not only expands upon the spectrum of genetic variations in CdLS, but also broadens our understanding of the clinical features of CdLS.

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Classic Cornelia de Lange syndrome with variant of unknown significance detected in NIPBL gene mutation: a case report

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-021-00142-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jay J. Desai ◽

Sreelata B. Nair ◽

S. Pappachan

Keyword(s):

Mental Retardation ◽

Clinical Features ◽

The Body ◽

Cornelia De Lange Syndrome ◽

Unknown Etiology ◽

Multiple Systems ◽

South Indian ◽

Indian Origin ◽

Unknown Significance ◽

Cornelia De Lange

Abstract Background Cornelia de Lange syndrome is a relatively uncommon disorder associated with multiple congenital anomalies/mental retardation of unknown etiology with its incidence varying from 1:10,000 to 1:50,000 live births in different population groups without any known racial predilections. Main clinical features of this syndrome consist of distinctive dysmorphic facial appearance, growth retardation, developmental delay, mental retardation, hirsutism, and skeletal formation anomaly. Case presentation This case presents a variation of unknown significance in the NIPBL gene-exon 39, chr5:37048649T>A c.6635T>A (p.Val2212Glu) with clinical phenotype of Cornelia de Lange syndrome. Our patient belonged to South Indian origin with clinical features of synophrys, micrognathia, long smooth philtrum, and clinodactyly with bilateral simian crease. Conclusion Cornelia de Lange syndrome is a rare but well-characterized disorder, in which multiple systems of the body are affected. It is important that the treating physician ensures coordination of the diversiform aspects of care in both childhood and adulthood. Proper and timely diagnosis using next generation sequencing helps in management and possibility of prenatal 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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The Cornelia de Lange syndrome

The Journal of Pediatrics ◽

10.1016/s0022-3476(63)80234-6 ◽

1963 ◽

Vol 63 (5) ◽

pp. 1000-1020 ◽

Cited By ~ 113

Author(s):

Louis J. Ptacek ◽

John M. Opitz ◽

David W. Smith ◽

Theo Gerritsen ◽

Harry A. Waisman

Keyword(s):

Cornelia De Lange Syndrome ◽

Cornelia De Lange

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