Classical Cornelia de Lange syndrome in a neonate

Cornelia de Lange syndrome is a rare developmental disorder syndrome involving multiple systems characterized by facial dysmorphism limb deformities, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities. The features of this disorder range from mild to severe. We present here a case of preterm newborn with Classical Cornelia de Lange syndrome with heterozygous mutation in NIBPL gene.

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Cornelia de Lange Syndrome A Case Report

Bangladesh Journal of Child Health ◽

10.3329/bjch.v44i1.49708 ◽

2020 ◽

Vol 44 (1) ◽

pp. 52-54

Author(s):

Muhammad Rezaul Karim ◽

Suraiya Begum ◽

Kohinoor Jahan Shamaly ◽

Ismot Ara Zannat

Keyword(s):

Short Stature ◽

Behavioral Problems ◽

Dna Analysis ◽

Cornelia De Lange Syndrome ◽

Heterozygous Mutation ◽

Facial Dysmorphism ◽

X Rays ◽

Multisystem Disorder ◽

Psychomotor Delay ◽

Cornelia De Lange

Cornelia de Lange syndrome (CdLS) is a rare syndrome of multisystem disorder. Almost every system is involved in this disorder having growth retardation, facial dysmorphism, short stature, psychomotor delay and behavioral problems. Diagnosis is made on the basis of clinical observations, physical examination, laboratory tests and X-rays; chromosome analysis is usually conducted before a diagnosis is made. DNA testing is helpful for confirmation of the clinical diagnosis. A 10 year old boy presented with short stature, facial dysmorphism, microcephaly, mental retardation and micromelia. DNA analysis revealed heterozygous mutation in NIBPL gene. Patient was counseled about the diagnosis and treatment was given. We reported the case due to rarity of the disease. Bangladesh J Child Health 2020; VOL 44 (1) :52-54

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Cornelia de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect

Nature Communications ◽

10.1038/s41467-021-23500-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Gabrielle Olley ◽

Madapura M. Pradeepa ◽

Graeme R. Grimes ◽

Sandra Piquet ◽

Sophie E. Polo ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Developmental Disorder ◽

Embryonic Stem ◽

Cornelia De Lange Syndrome ◽

Gene Encoding ◽

Cornelia De Lange ◽

Dna Damage Signalling ◽

Repair Defect ◽

Mutant Cells

AbstractCornelia de Lange syndrome is a multisystem developmental disorder typically caused by mutations in the gene encoding the cohesin loader NIPBL. The associated phenotype is generally assumed to be the consequence of aberrant transcriptional regulation. Recently, we identified a missense mutation in BRD4 associated with a Cornelia de Lange-like syndrome that reduces BRD4 binding to acetylated histones. Here we show that, although this mutation reduces BRD4-occupancy at enhancers it does not affect transcription of the pluripotency network in mouse embryonic stem cells. Rather, it delays the cell cycle, increases DNA damage signalling, and perturbs regulation of DNA repair in mutant cells. This uncovers a role for BRD4 in DNA repair pathway choice. Furthermore, we find evidence of a similar increase in DNA damage signalling in cells derived from NIPBL-deficient individuals, suggesting that defective DNA damage signalling and repair is also a feature of typical Cornelia de Lange syndrome.

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Cornelia De Lange Syndrome in Iraq

Clinical Medical Reviews and Reports ◽

10.31579/2690-8794/010 ◽

2020 ◽

Vol 2 (02) ◽

pp. 01-04

Author(s):

Aamir Mosawi

Keyword(s):

Mental Retardation ◽

Male Patient ◽

Growth Retardation ◽

Cornelia De Lange Syndrome ◽

Facial Dysmorphism ◽

Upper Lip ◽

Nasal Bridge ◽

Short Nose ◽

Convergent Squint ◽

Cornelia De Lange

Background: Cornelia de Lange syndrome is a rare syndrome of highly variable phenotype making a spectrum ranging from classic syndrome with many cardinal features to mild condition few cardinal features. Typically patients with classic syndrome had growth and mental retardation and distinctive facial dysmorphism including thick (bushy) and / or long eyebrows commonly with synophrys, short nose with depressed or concave nasal bridge and/or upturned nasal tip , long or smooth or indistinct philtrum, thin upper lip vermilion and/or downturned corners of mouth, and low set ears. The diagnosis of the syndrome is clinical. Ocular abnormalities that can be associated with Cornelia de Lang syndrome squint, nystagmus, refractive errors, and ptosis. Materials and methods: The occurrence of Cornelia de Lange syndrome has not been reported or well-documented. The first four Iraqi patients (Three boys and one girl) with Cornelia de Lange syndrome are described. The relevant literatures were reviewed with aim of determining the early documentation of the syndrome in the medical literatures. Results: All the patients were sporadic cases and had growth retardation, severe mental retardation with significant developmental delay, thick eye brows with some degree of synophrys, short nose with depressed or concave nasal bridge, and low set ears. All the patients had normal karyotype. One male patient had all of the classical features including long smooth and indistinct philtrum, thin upper lip vermilion, and downturned corners of mouth. The second male patient had a concave nasal bridge that becomes more obvious during crying, nystagmus and bilateral convergent squint. The third boy had milder dysmorphic features. The fourth patient was a girl who was the second of a twin. She had severe growth retardation and was hypotonic with poor head control. She also had bilateral convergent squint, refractive error, and reduction in visual acuity. Conclusion: The first four Iraqi patients with Cornelia de Lang syndrome are reported.

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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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Gambaran Perkembangan Komunikasi Anak Cornelia de Lange Syndrome (CdLS)

Jurnal Ilmu Keperawatan Anak ◽

10.32584/jika.v2i1.179 ◽

2019 ◽

Vol 2 (1) ◽

pp. 27

Author(s):

Tri Retno Indah Susanti ◽

Meira Erawati ◽

Dwi Retno Nurniningsih

Keyword(s):

Play Therapy ◽

Developmental Disorders ◽

Developmental Disorder ◽

Language Use ◽

Speech Therapy ◽

Cornelia De Lange Syndrome ◽

Communication Development ◽

Cornelia De Lange ◽

Minor Criteria

Cornelia de Lange Syndrome (CdLS) adalah gangguan perkembangan multisistem yang dikaitkan dengan gangguan kognitif, malformasi dan gangguan wajah internal yang khas. Gangguan perkembangan yang terjadi pada Cornelia de Lange Syndrome (CdLS) adalah keterampilan berbahasa dan berbicara. Tujuan dari penelitian ini adalah melihat peningkatan perkembangan komunikasi anak Sindrom Cornelia de Lange (CdLS) setelah diberi intervensi play therapy dan terapi wicaradengan menggunakan media gambar dan warna. Metodologi penelitian ini menggunakan desain studi kasus. Alat yang digunakan untuk mengukur kemampuan bahasa menggunakan DENVER II. Berdasarkan hasil penelitian pada 9 November 2018, anak berusia 3 tahun, 9 bulan, 3 hari dengan diagnosis medis Sindrom Cornelia de Lange (CdLS) dengan keluhan anak belum bisa bicara. Hasil pemeriksaan fisik menunjukkan terdapat bentuk khas yaitu alis mata menyatu ditengah, bulu mata panjang, terdapat juga kriteria minor. Hasil pemeriksaan DENVER II dari bahasa, anak masih seperti anak usia 18 bulan. Berdasarkan hasil evaluasi setelah 1 bulan tindakan keperawatan dan kolaborasi dengan terapis, telah terjadi peningkatan komunikasi anak.Kata kunci: Cornelia de Lang Syndrome, Peningkatan perkembangan, terapi wicara.Description of Communication Development in Children with Cornelia De Lange Syndrome (Cdls)AbstractCornelia de Lange Syndrome (CdLS) is a multisystem developmental disorder that is associated with cognitive impairments, malformations and internal and typical facial disorders. Developmental disorders that occur in Cornelia de Lange Syndrome (CdLS) are language skills and speech. The purpose of this study was to see the speed of communication development of children of Cornelia de Lange Syndrome (CdLS), after being given an intervention. Improve conversation by using play therapy using image and color media. The methodology of this research uses case study design. The tool used to measure the ability language use the DENVER II. Based on the results of the study on November 9, 2018, children aged 3 years, 9 months, 3 days with a medical diagnosis of Cornelia de Lange Syndrome (CdLS) were obtained with a comparison of children unable to speak. From the results of physical examination, there are typical forms, namely spies in the middle, long eyelashes, also there are minor criteria. The results of DENVER II examination of various children's languages are still like 18 months old children. Based on the evaluation results after 1 month of nursing actions and collaboration with the therapist, there has been an increase in communication of children with Cornelia de Lange Syndrome (CdLS).Key words: Cornelia de Lang Syndrome, Increased development, Speech therapy

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De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome

Medicina ◽

10.3390/medicina56020076 ◽

2020 ◽

Vol 56 (2) ◽

pp. 76

Author(s):

Duong Chi Thanh ◽

Can Thi Bich Ngoc ◽

Ngoc-Lan Nguyen ◽

Chi Dung Vu ◽

Nguyen Van Tung ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

De Novo ◽

Cornelia De Lange Syndrome ◽

Heterozygous Mutation ◽

Body Parts ◽

Efficient Tool ◽

Whole Exome ◽

Cornelia De Lange ◽

In Silico Analyses

Cornelia de Lange Syndrome (CdLS) is a rare congenital genetic disease causing abnormal unique facial phenotypes, several defects in organs and body parts, and mental disorder or intellectual disorder traits. Main causes of CdLS have been reported as variants in cohesin complex genes, in which mutations in the NIPBL gene have been estimated to account for up to 80%. Our study included three Vietnamese patients with typical CdLS phenotypes. Whole exome sequencing revealed two known heterozygous mutations c.6697G>A (p.Val2233Met) and c.2602C>T (p.Arg868X), and a novel heterozygous mutation c.4504delG (p.Val1502fsX87) in the NIPBL gene of the three patients. In silico analyses of the identified mutations predicted possible damaging and truncating effects on the NIPBL protein. Inherited analyses in the patients’ families showed that all of the mutations are de novo. Our results lead a definitive diagnosis of patients with CdLS and expand the spectrum of mutations in the NIPBL gene. These findings also confirm whole exome sequencing is an efficient tool for genetic screening of CdLS.

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Cornelia de Lange syndrome in children

Health and Ecology Issues ◽

10.51523/2708-6011.2016-13-3-22 ◽

2016 ◽

pp. 102-107

Author(s):

T. E. Bubnevich

Keyword(s):

Mental Retardation ◽

Upper Limb ◽

Growth Retardation ◽

Postnatal Growth ◽

Cornelia De Lange Syndrome ◽

Facial Dysmorphism ◽

Malformation Syndrome ◽

Postnatal Growth Retardation ◽

Live Births ◽

Cornelia De Lange

Cornelia de Lange syndrome is a multisystem malformation syndrome recognized primarily on the basis of characteristic facial dysmorphism, including low anterior hairline, arched eyebrows, synophrys, anteverted nares, maxillary prognathism, thin lips, «carp» mouth, in association with prenatal and postnatal growth retardation, mental retardation and, in many cases, upper limb anomalies. However, there are clinical options with milder phenotypes in this syndrome. The prevalence of the syndrome is 1:10,000-30,000 live births, occurs equally, regardless of gender. Although this syndrome is considered rare, experts agree that it is likely underdiagnosed.

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Cornelia de Lange Syndrome as Paradigm of Chromatinopathies

Frontiers in Neuroscience ◽

10.3389/fnins.2021.774950 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ilaria Parenti ◽

Frank J. Kaiser

Keyword(s):

Transcriptional Regulation ◽

Chromatin Remodeling ◽

Neurodevelopmental Disorders ◽

Molecular Mechanisms ◽

Cornelia De Lange Syndrome ◽

Facial Dysmorphism ◽

Behavioral Disturbances ◽

Chromatid Cohesion ◽

Topologically Associated Domains ◽

Cornelia De Lange

Chromatinopathies can be defined as a class of neurodevelopmental disorders caused by mutations affecting proteins responsible for chromatin remodeling and transcriptional regulation. The resulting dysregulation of gene expression favors the onset of a series of clinical features such as developmental delay, intellectual disability, facial dysmorphism, and behavioral disturbances. Cornelia de Lange syndrome (CdLS) is a prime example of a chromatinopathy. It is caused by mutations affecting subunits or regulators of the cohesin complex, a multisubunit protein complex involved in various molecular mechanisms such as sister chromatid cohesion, transcriptional regulation and formation of topologically associated domains. However, disease-causing variants in non-cohesin genes with overlapping functions have also been described in association with CdLS. Notably, the majority of these genes had been previously found responsible for distinct neurodevelopmental disorders that also fall within the category of chromatinopathies and are frequently considered as differential diagnosis for CdLS. In this review, we provide a systematic overview of the current literature to summarize all mutations in non-cohesin genes identified in association with CdLS phenotypes and discuss about the interconnection of proteins belonging to the chromatinopathies network.

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