scholarly journals Clinical and molecular analysis in a cohort of Chinese children with Cornelia de Lange syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Qun Li ◽  
Guoying Chang ◽  
Lei Yin ◽  
Juan Li ◽  
Xiaodong Huang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Genetic Variations ◽  
Chinese Children ◽  
Chinese Patients ◽  
Cornelia De Lange Syndrome ◽  
Gene Variants ◽  
Wide Range ◽  
Cornelia De Lange

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.

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.

scholarly journals Case Report: Novel NIPBL Variants Cause Cornelia de Lange Syndrome in Chinese Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Peng ◽  
Changbiao Liang ◽  
Hui Xi ◽  
Shuting Yang ◽  
Jiancheng Hu ◽  
...  
Keyword(s):  
Growth Retardation ◽  
De Novo ◽  
Genetic Disorder ◽  
Snp Array ◽  
Nuchal Translucency ◽  
Chinese Patients ◽  
Cornelia De Lange Syndrome ◽  
Whole Exome ◽  
Limb Malformations ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. Mutation in the NIPBL gene accounts for nearly 60% of the cases. This study reports the clinical and genetic findings of three cases of CdLS from unrelated Chinese families. Clinically, all the three cases were classified as classic CdLS based on the cardinal (distinctive facial features and limb malformations) and suggestive (developmental delay, growth retardation, microcephaly, hirsutism, etc.) manifestations. SNP array detected a novel de novo heterozygous microdeletion of 0.2 Mb [arr[GRCh37]5p13.2(36848530_37052821) × 1] that spans the first 43 exons of NIPBL in the fetus with nuchal translucency thickening in case 1. Whole-exome sequencing in family trios plus Sanger sequencing validation identified a de novo heterozygous NIPBL c.5566G>A (p.R1856G) mutation in the fetus with intrauterine growth retardation in case 2 and a novel de novo heterozygous NIPBL c.448dupA (p.S150Kfs*23) mutation in the proband (an 8-month-old girl) in case 3. The cases presented in this study may serve as references for increasing our understanding of the mutation spectrum of NIPBL in association with CdLS.

scholarly journals A Chinese Case of Cornelia de Lange Syndrome Caused by a Pathogenic Variant in SMC3 and a Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Ran Li ◽  
Bowen Tian ◽  
Hanting Liang ◽  
Meiping Chen ◽  
Hongbo Yang ◽  
...  
Keyword(s):  
Literature Review ◽  
Short Stature ◽  
Clinical Manifestations ◽  
Pathogenic Variant ◽  
Cornelia De Lange Syndrome ◽  
Gene Variants ◽  
Whole Exome ◽  
Development Delay ◽  
Cornelia De Lange ◽  
Verbal Development

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.

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.

Cornelia De Lange Syndrome with Additional Clinical Features and Multicystic Kidney Disease

2013 ◽  
Vol 81 (2) ◽  
pp. 194-195 ◽  
Author(s):  
Jaiprakash Narayan Meghwal ◽  
Achala Arya ◽  
B. S. Karnawat ◽  
Suchitra Narayan
Keyword(s):  
Kidney Disease ◽  
Clinical Features ◽  
Cornelia De Lange Syndrome ◽  
Multicystic Kidney ◽  
Cornelia De Lange ◽  
Multicystic Kidney Disease

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

2007 ◽  
Vol 28 (2) ◽  
pp. 205-206 ◽  
Author(s):  
Guntram Borck ◽  
Mohamed Zarhrate ◽  
Jean-Paul Bonnefont ◽  
Arnold Munnich ◽  
Valérie Cormier-Daire ◽  
...  
Keyword(s):  
Clinical Features ◽  
Cornelia De Lange Syndrome ◽  
Cornelia De Lange

scholarly journals Hashimoto encephalopathy: A study of the clinical profile, radiological and electrophysiological correlation in a Tertiary Care Center in South India

2015 ◽  
Vol 6 (03) ◽  
pp. 309-314 ◽  
Author(s):  
Pattanagere Manjunatha Suryanarayana Sharma ◽  
Mahendra Javali ◽  
Rohan Mahale ◽  
Byadarahalli Kempegowda Madhusudhan ◽  
Anas Abdul Majeed ◽  
...  
Keyword(s):  
Clinical Features ◽  
Clinical Laboratory ◽  
Tertiary Care ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Thyroid Peroxidase ◽  
Radiologic Findings ◽  
Hashimoto Encephalopathy ◽  
Wide Range ◽  
Clinical Series

Abstract Background: Hashimoto encephalopathy (HE) is a poorly understood and often misdiagnosed entity with variable clinical spectrum. There are many uncertainties that still remain about this condition and the pathological significance of thyroid peroxidase (TPO) antibody. Objective: To characterize the clinical, laboratory and radiologic findings in patients with HE. Design: Retrospective analysis of clinical features and diagnostic test data. Main Outcome Measures: Clinical features, laboratory, radiologic, electroencephalography (EEG) findings associated with HE and therapeutic outcome. Results: Thirteen consecutive patients were identified as having HE. The median age at onset was 48.5 years (range, 19-62 years). There was a female preponderance (76.9%). Clinical manifestations were cognitive impairment and behavioral changes in 10 (76.9%), sleep disturbance in 9 (69.2%), seizures in 6 (46.1%), headache in 4 (30.8%), psychosis or paranoia in 5 (38.5%), transient symptoms in 6 (46.1%), myoclonus in 4 (30.8%), ataxia or gait disorder in 4 (30.8%). The most frequent laboratory abnormalities were increased TPO (n = 13) in all cases, increased thyroid stimulating hormone levels (n = 6), and increased erythrocyte sedimentation rate (n = 5). The cerebrospinal fluid protein level was elevated in 8 of 9 patients (88.8%). Magnetic resonance imaging abnormalities were present in 2 patients (15.4%). EEG changes were seen in 7 patients (53.8%). All but two patients showed significant therapeutic benefit with steroids. Conclusions: HE has a wide range of clinical, laboratory, and radiologic findings. All patients with an unexplained encephalopathy should be screened for this condition as treatment response is excellent. To the best of our knowledge, this is the largest single center clinical series of HE from the Indian subcontinent.

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 A rare presentation of KBG syndrome

2021 ◽  
Vol 8 (7) ◽  
pp. 1284
Author(s):  
Dhanya Soodhana Mohan ◽  
Vani Hebbal Nagarajappa
Keyword(s):  
Cognitive Impairment ◽  
Clinical Features ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Genetic Condition ◽  
Rare Presentation ◽  
Characteristic Appearance ◽  
The Third ◽  
Wide Range ◽  
Kbg Syndrome

KBG syndrome is a rare, genetic disorder characterizedby cognitive impairment, short stature, skeletal (mainly costovertebral) anomalies and a distinct craniofacial appearance. It is usually autosomal dominant in nature with a wide range of expressivity in its clinical features. We describe what appears to be the third case reported from India.The aim of this article is to review familiar clinical features and to highlight the endocrine management of KBG syndrome. We are hereby reporting a case of 17 year 10 months old adolescent who had neurocognitive impairment and a characteristic appearance, which led to the diagnosis of this genetic condition.

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