scholarly journals A 16-Day-Old Infant with a Clinical Diagnosis of Classical Cornelia de Lange Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Pamela Rodríguez ◽  
Karla Asturias
Keyword(s):  
Clinical Diagnosis ◽  
Genetic Disorder ◽  
Molecular Genetic ◽  
Male Infant ◽  
Cornelia De Lange Syndrome ◽  
Clinical Criteria ◽  
Limb Reduction ◽  
Regulator Genes ◽  
Craniofacial Features ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CdLS) is a rare syndromic genetic disorder characterized by multiple congenital anomalies with upper limb reduction defects, along with cardiac, gastrointestinal, and genitourinary defects. It is caused by genetic variations in the chromatin regulator genes, most commonly, the cohesin complex. Even though molecular genetic testing is highly recommended to confirm the diagnosis, high costs and unavailability in some settings are significant setbacks, and clinical criteria could be used. The typical craniofacial features include generalized hirsutism, synophrys, microbrachycephaly, highly arched eyebrows, and long eyelashes, along with height and weight below the 5th percentile. In this paper, we present a case of a 16-day-old male infant in whom a clinical diagnosis of classical CdLS was made.

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

Diagnostics ◽  
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.

scholarly journals Diphenhydramine-Refractory Antipsychotic-Induced Dystonia in an Adolescent Male With Cornelia de Lange Syndrome

2019 ◽  
Vol 24 (2) ◽  
pp. 160-165 ◽  
Author(s):  
Stephen M. Small ◽  
Rachel S. Bacher
Keyword(s):  
Emergency Department ◽  
First Generation ◽  
Case Reports ◽  
Genetic Disorder ◽  
Cornelia De Lange Syndrome ◽  
Adolescent Male ◽  
Qtc Interval ◽  
Drug Induced ◽  
Iatrogenic Complications ◽  
Cornelia De Lange

Cornelia de Lange Syndrome is a rare genetic disorder that results in distinctive craniofacial deformities, developmental delay, hirsutism, and other physical abnormalities. Case reports suggest some of these patients exhibit sensitivity and paradoxical reactions to certain psychoactive drugs. This report of a 16-year-old male with Cornelia de Lange is the first to describe dystonia from a first-generation antipsychotic that did not respond to conventional treatment with diphenhydramine. The patient initially presented to the Emergency Department for agitation, which progressively worsened after administration of diphenhydramine, olanzapine, and intramuscular haloperidol. The patient returned to the Emergency Department the following day because of altered mental status and lethargy that progressed to periodic lip-smacking movements and contraction of his upper extremities. His symptoms continued despite administration of diphenhydramine and loading doses of 3 antiepileptic drugs. His abnormal labs included an elevated creatine kinase and a prolonged QTc interval on his electrocardiogram. His symptoms were later deemed a probable drug-induced dystonic reaction to haloperidol once seizures were excluded by an unremarkable electroencephalogram. This case supports previous reports suggesting an association between Cornelia de Lange and paradoxical drug reactions, and it is recommended that clinicians strongly weigh the risks of prescribing first-generation antipsychotics for this patient population. These medications should be carefully titrated, with close patient monitoring to prevent adverse drug effects and other iatrogenic complications because antidotes may be rendered ineffective by this condition.

First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia

2019 ◽  
Vol 72 (8) ◽  
pp. 558-561 ◽  
Author(s):  
Grazia Fazio ◽  
Valentina Massa ◽  
Andrea Grioni ◽  
Vojtech Bystry ◽  
Silvia Rigamonti ◽  
...  
Keyword(s):  
Paediatric Patient ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Genetic Disorder ◽  
Premature Stop Codon ◽  
Cornelia De Lange Syndrome ◽  
Sequencing Analysis ◽  
First Case ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant genetic disorder characterised by prenatal and postnatal growth and mental retardation, facial dysmorphism and upper limb abnormalities. Germline mutations of cohesin complex genes SMC1A, SMC3, RAD21 or their regulators NIPBL and HDAC8 have been identified in CdLS as well as somatic mutations in myeloid disorders. We describe the first case of a paediatric patient with CdLS with B-cell precursor Acute Lymphoblastic Leukaemia (ALL). The patient did not show any unusual cytogenetic abnormality, and he was enrolled into the high risk arm of AIEOP-BFM ALL2009 protocol because of slow early response, but 3 years after discontinuation, he experienced an ALL relapse. We identified a heterozygous mutation in exon 46 of NIPBL, causing frameshift and a premature stop codon (RNA-Targeted Next generation Sequencing Analysis). The analysis of the family indicated a de novo origin of this previously not reported deleterious variant. As for somatic cohesin mutations in acute myeloid leukaemia, also this ALL case was not affected by aneuploidy, thus suggesting a major impact of the non-canonical role of NIPBL in gene regulation. A potential biological role of NIPBL in leukaemia has still to be dissected.

Clinical Diagnosis of Classical Cornelia de Lange Syndrome Made From Postmortem Examination of Second Trimester Fetus With Novel NIPBL Pathogenic Variant

2019 ◽  
Vol 22 (5) ◽  
pp. 475-479 ◽  
Author(s):  
Jennifer Hague ◽  
Philip Twiss ◽  
Zoe Mead ◽  
Soo-Mi Park
Keyword(s):  
Clinical Diagnosis ◽  
Upper Limb ◽  
Growth Retardation ◽  
Postmortem Examination ◽  
Pathogenic Variant ◽  
Cornelia De Lange Syndrome ◽  
Molecular Testing ◽  
Intrauterine Death ◽  
Second Trimester ◽  
Cornelia De Lange

Classical Cornelia de Lange syndrome (CdLS) is a rare genetic disorder which is associated with distinctive facial features, growth retardation, significant intellectual disability and global developmental delay, hirsutism, and upper-limb reduction defects. Classical CdLS is associated with pathogenic variants in NIPBL. We present a clinical diagnosis of classical CdLS made in a second trimester male fetus with advanced maceration who had undergone intrauterine death at 15 + 6 weeks gestation. The diagnosis was suspected after multiple congenital anomalies were identified on fetal postmortem examination. These included intrauterine growth retardation, upper limb anomalies, ventricular septal defect and diaphragmatic hernia, and skeletal and genitourinary abnormalities. Related prenatal screening findings included a raised nuchal translucency and low maternal serum pregnancy-associated plasma protein-A. Targeted molecular sequencing of genes associated with CdLS identified a novel de novo frameshift pathogenic variant in NIPBL, which confirmed the diagnosis. This report describes our case and reviews the current literature on prenatal diagnosis of CdLS. In summary, we demonstrate that clinical diagnosis of CdLS in a second trimester fetus, through postmortem examination findings, is possible, with confirmation through molecular testing.

scholarly journals Brachmann Cornelia De Lange Syndrome: A Tailored Approach for Assessment and Intervention Using the Griffiths III

2020 ◽  
Vol 10 (3) ◽  
pp. 43
Author(s):  
Jennifer M Jansen ◽  
Elizabeth Mary Green ◽  
Louise A Stroud ◽  
Mark B Watson
Keyword(s):  
Test Scores ◽  
Genetic Disorder ◽  
Intervention Strategy ◽  
Clinical Population ◽  
Cornelia De Lange Syndrome ◽  
Level Of Functioning ◽  
Intervention Plan ◽  
Developmental Functioning ◽  
Tailored Approach ◽  
Cornelia De Lange

The process of evaluation and intervention of an atypical child poses challenges in a number of areas. These challenges include measures that are not normed for a clinical population, the interpretation of test scores and the use of test scores to devise a meaningful individualized intervention plan that also takes into account sociocultural issues affecting family functioning. To highlight these challenges, an evaluation of a 7-year 1month old girl with Brachmann Cornelia De Lange Syndrome is described using the Griffiths III Scales of Child Development together with the Conners 3- Parent Teacher Surveys and the Vineland Adaptive Scales. The Griffiths III results confirmed a pattern of global delay in all areas of her developmental functioning. The child demonstrated difficulty with the medical and behavioural manifestations of her genetic disorder that needed to be factored into the intervention strategy. The results guided the interventions of different professionals in developing an individualised intervention plan considering the above-identified challenges. The article serves thus as a guide on how to work creatively to determine the level of functioning of an atypical child in the light of the absence of normed measures for such children.

scholarly journals Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes

2020 ◽  
Vol 21 (3) ◽  
pp. 1042 ◽  
Author(s):  
Ana Latorre-Pellicer ◽  
Ángela Ascaso ◽  
Laura Trujillano ◽  
Marta Gil-Salvador ◽  
Maria Arnedo ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Prediction Accuracy ◽  
Genetic Diseases ◽  
Clinical Score ◽  
Cornelia De Lange Syndrome ◽  
Computer Assisted ◽  
Causal Genes ◽  
Facial Pattern ◽  
Computer Assisted Image ◽  
Cornelia De Lange

Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.

A Novel Mutation in NIPBL Gene with the Cornelia de Lange Syndrome and a 10q11.22-q11.23 Microdeletion in the Same Individual

2020 ◽  
Author(s):  
Haydar Bağış ◽  
Özden Öztürk ◽  
Semih Bolu ◽  
Bayram Taşkın
Keyword(s):  
Novel Mutation ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
The Other ◽  
Cornelia De Lange Syndrome ◽  
Other Hand ◽  
Wide Range ◽  
Cornelia De Lange

AbstractThe Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL, SMC1A, SMC3, RAD21, and HDAC8. On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study

2014 ◽  
Vol 31 (1) ◽  
pp. 141-146 ◽  
Author(s):  
Fernando Chico-Ponce de León ◽  
Luis F. Gordillo-Domínguez ◽  
Vicente González-Carranza ◽  
Samuel Torres-García ◽  
Constanza García-Delgado ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Single Case ◽  
Molecular Genetic ◽  
Cornelia De Lange Syndrome ◽  
Single Case Study ◽  
Genetic Characteristics ◽  
Cornelia De Lange

scholarly journals An Autosomal Recessive form of Cornelia de Lange Syndrome Due to Mutations in TRMT61A Gene: A Case Report

2020 ◽  
pp. 327-331
Author(s):  
Fadel A. Sharif
Keyword(s):  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Missense Variant ◽  
Cornelia De Lange Syndrome ◽  
Rna Modification ◽  
Compound Heterozygous ◽  
Specific Pcr ◽  
Gastrointestinal Problems ◽  
Cornelia De Lange ◽  
Coding Variants

Background: Cornelia de Lange syndrome is a rare genetic disorder presenting with craniofacial dysmorphia, developmental delay, intellectual disabilities, upper limb abnormalities and gastrointestinal problems. The disease is genetically heterogenous and the underlying genetic cause in unknown in around 30% of the cases. Case Presentation: A Palestinian family visited our department for genetic counseling. The non-consanguineous parents have only two (4 and 2 years old) daughters, both presented with features consistent with Cornelia de Lange syndrome. Whole exome sequencing revealed two previously unknown coding variants in the autosomal TRMT61A, a gene that has not been linked to any human disease before. TRMT61A codes for the catalytic subunit of tRNA (adenine-N1-)-methyltransferase. The mother harbored an in-frame deletion variant c.478_483delCGCACC (p.R160_T161del), whereas the father carried a missense variant c.323G>T (p.C108F). Both variants are novel and were predicted as "damaging". So far, no autosomal recessive forms of the disease has been described in the literature. The carrier states of the parents and the existence of the two variants in compound heterozygous forms in both girls was further confirmed by allele-specific PCR. In their next pregnancy, prenatal diagnosis indicated that the fetus is a carrier of the mother's variant and the pregnancy culminated in the birth of a healthy baby girl. Conclusion: It can be concluded that the TRMT61A mutations are the cause of the disease features observed in this family and supports the proposal that RNA modification defects are involved in the molecular pathogenesis of Cornelia de Lange syndrome.

scholarly journals Case Report: Atypical Cornelia de Lange Syndrome

F1000Research ◽  
2015 ◽  
Vol 3 ◽  
pp. 33
Author(s):  
Vito Leanza ◽  
Gabriella Rubbino ◽  
Gianluca Leanza
Keyword(s):  
Genetic Disorder ◽  
Normal Karyotype ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Cornelia De Lange Syndrome ◽  
Saddle Nose ◽  
Nasal Bridge ◽  
Venous Dilatation ◽  
Cornelia De Lange ◽  
Increased Nuchal Translucency

Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation.We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy.

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