De NovoTrisomy 1q10q23.3 Mosaicism Causes Microcephaly, Severe Developmental Delay, and Facial Dysmorphic Features but No Cardiac Anomalies

Proximal duplications of chromosome 1q are rare chromosomal abnormalities. Most patients with this condition present with neurological, urogenital, and congenital heart disease and short life expectancy. Mosaicism for trisomy 1q10q23.3 has only been reported once in the literature. Here we discuss a second case: a girl with a postnatal diagnosis of ade novopure mosaic trisomy 1q1023.3 who has no urogenital or cardiac anomalies.

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Interstitial Deletion of 2q22.2q22.3 Involving the Entire ZEB2 Gene in a Case of Mowat-Wilson Syndrome

Molecular Syndromology ◽

10.1159/000513313 ◽

2021 ◽

pp. 1-9

Author(s):

Khaled Refaat ◽

Nivine Helmy ◽

Mohamed Elawady ◽

Mona El Ruby ◽

Alaa Kamel ◽

...

Keyword(s):

Congenital Heart ◽

Autosomal Dominant ◽

De Novo ◽

Pulmonary Arteries ◽

Hirschsprung Disease ◽

Research Centre ◽

Chromosomal Microarray ◽

Facial Dysmorphism ◽

Dysmorphic Features ◽

Human Cytogenetics

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the ZEB2 gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA). A 1-year-old male child was referred to the CHD clinic, National Research Centre, presenting with dysmorphic features and CHD. The patient was referred to the human cytogenetics department for cytogenetic analysis and for screening of subtelomere rearrangements and microdeletion loci, using MLPA, and all revealed normal results. CMA revealed an interstitial 2.27-Mb microdeletion in chromosome 2q, involving the entire ZEB2 gene and other genes. This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in patients presenting with the characteristic facial dysmorphism, developmental delay, seizures, Hirschsprung disease, and congenital heart anomalies, especially those involving the pulmonary arteries or pulmonary valves. It is recommended to include the ZEB2 locus in the MLPA microdeletions probes.

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Deletion of 15q26.1 region with absence epilepsy respond to valproic acid: A Literature Overview and A Case Report from Qatar

International Journal of Case Reports ◽

10.28933/ijcr-2021-03-3005 ◽

2021 ◽

pp. 210

Author(s):

Keyword(s):

Developmental Disorders ◽

De Novo ◽

Chromosomal Abnormalities ◽

Intractable Epilepsy ◽

Absence Epilepsy ◽

Growth Delay ◽

Comparative Genomic ◽

Potential Candidate ◽

Speech Delay ◽

Dysmorphic Features

Chromosomal abnormalities involving deletions and duplications are known to cause severe developmental disorders, including mental retardation, dysmorphism, and seizures, in children. As the technique of array-based comparative genomic hybridization is being applied more frequently in the diagnostic evaluation of children with developmental disorders; novel pathologic chromosomal abnormalities are being identified in relation to various type of epilepsies in childhood. We report the case of a 4-year-old girl with a history of speech delay and communication disorder, mild dysmorphic features, and absence epilepsy with a de novo microdeletion 15q26.1. A much larger (5 Mb) but overlapping microdeletion has been previously reported in similar several cases with similar phenotype including intractable myoclonic and absence epilepsy, growth delay, and dysmorphic features. This leads us to propose that a potential candidate gene or genes within the deleted region involved in the pathogenesis of some forms of generalized intractable epilepsy, previously considered idiopathic should consider genetic study for childhood epilepsies especially if it was associated with underlying developmental delay in any particular aspect as speech delay in our case.

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Atypical Fetal Hydantoin Syndrome

PEDIATRICS ◽

10.1542/peds.70.2.327 ◽

1982 ◽

Vol 70 (2) ◽

pp. 327-327

Author(s):

Mark S. Lubinsky

Keyword(s):

De Novo ◽

Chromosomal Abnormalities ◽

Chromosome 17 ◽

Dysmorphic Features

The pattern of malformations observed by Bartoshesky et al1 is atypical for fetal hydantoin syndrome, suggesting the possibility of an additional teratogenic influence. No mention was made of chromosome studies, either blood or tissue, in the infant, and the possibility of aneuploidy should be considered. I have seen two children with de novo chromosomal abnormalities whose mothers had been on anticonvulsants. The first, the daughter of a mother taking hydantoin, had dysmorphic features and extra chromosomal material of uncertain origin attached to the short arm of chromosome 17. Both parents had normal karyotypes.

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Multiple Coronary Artery Microfistulas in a Girl with Kleefstra Syndrome

Case Reports in Genetics ◽

10.1155/2016/3056053 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5

Author(s):

Euthymia Vargiami ◽

Athina Ververi ◽

Hamda Al-Mutawa ◽

Georgia Gioula ◽

Spyridon Gerou ◽

...

Keyword(s):

Coronary Artery ◽

Developmental Delay ◽

Congenital Heart Defects ◽

Congenital Heart ◽

De Novo ◽

Heart Defects ◽

Dysmorphic Features ◽

Kleefstra Syndrome

Kleefstra syndrome is characterized by hypotonia, developmental delay, dysmorphic features, congenital heart defects, and so forth. It is caused by 9q34.3 microdeletions orEHMT1mutations. Herein a 20-month-old girl with Kleefstra syndrome, due to a de novo subterminal deletion, is described. She exhibits a rare and complex cardiopathy, encompassing multiple coronary artery microfistulas, VSD/ASD, and PFO.

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De Novo Damaging Variants, Clinical Phenotypes, and Post-Operative Outcomes in Congenital Heart Disease

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.119.002836 ◽

2020 ◽

Vol 13 (4) ◽

Author(s):

Marko T. Boskovski ◽

Jason Homsy ◽

Meena Nathan ◽

Lynn A. Sleeper ◽

Sarah Morton ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Heart Surgery ◽

De Novo ◽

Open Heart Surgery ◽

Copy Number Variants ◽

Hazard Ratio ◽

Free Survival ◽

Cardiac Anomalies

Background: De novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown. Methods: We studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network). Results: Two hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies ( P =5.63×10 −12 ). In 1268 patients (50.4%) who had surgical data available and underwent open-heart surgery exclusive of heart transplantation as their first operation, we analyzed transplant-free survival following the first operation. Median follow-up was 2.65 years. De novo variants were associated with worse transplant-free survival (hazard ratio, 3.51; P =5.33×10 −04 ) and longer times to final extubation (hazard ratio, 0.74; P =0.005). As de novo variants had a significant interaction with extra-cardiac anomalies for transplant-free survival ( P =0.003), de novo variants conveyed no additional risk for transplant-free survival for patients with these anomalies (adjusted hazard ratio, 1.96; P =0.06). By contrast, de novo variants in patients without extra-cardiac anomalies were associated with worse transplant-free survival during follow-up (hazard ratio, 11.21; P =1.61×10 −05 ) than that of patients with no de novo variants. Using agnostic machine-learning algorithms, we identified de novo copy number variants at 15q25.2 and 15q11.2 as being associated with worse transplant-free survival and 15q25.2, 22q11.21, and 3p25.2 as being associated with prolonged time to final extubation. Conclusions: In patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01196182.

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A very rare partial trisomy syndrome: De novo duplication of 16q12.1q23.3 in a Turkish girl with developmental delay and facial dysmorphic features

Balkan Journal of Medical Genetics ◽

10.2478/bjmg-2020-0009 ◽

2020 ◽

Vol 23 (1) ◽

pp. 103-108

Author(s):

A Türkyılmaz ◽

O Yaralı

Keyword(s):

Developmental Delay ◽

De Novo ◽

Chromosomal Abnormalities ◽

Chromosomal Translocation ◽

Partial Trisomy ◽

Clinical Findings ◽

Comparative Genomic ◽

Dysmorphic Features ◽

Autosomal Trisomy ◽

Metopic Suture

AbstractTrisomy 16 is the most common type of autosomal trisomy associated with spontaneous abortion and is incompatible with life. Upon examining previously reported cases of partial chromosome 16q duplication, it was noted that the majority of cases had complex chromosomal abnormalities due to parental balanced chromosomal translocation carriage. The clinical presentation of very rare pure partial trisomy 16q cases was associated with congenital anomalies, facial dysmorphic findings and intellectual disability. In this study, we evaluated the physical characteristics and genetic data of an 8-month-old girl with developmental delay and facial dysmorphic features. Dysmorphic features including prominent metopic suture, synophrys, asymmetric head shape, triangular and asymmetric face, telecanthus, epicanthal folds, down-slanting palpebral fissures, microphthalmia of the left eye, anteverted nares, smooth and tented philtrum, microretrognathia, low-set posteriorly rotated ears, auricular pits, high-arched palate, thin upper lip and hypotonia were recorded. Her karyotype was 46,XX,add(16)(q24). To identify the extension of the duplicated section, array comparative genomic hybridization (aCGH) analysis was performed, which showed a de novo 29.8 Mb duplication [arr[hgl9] 16q12.1q23.3(52459169-82285105) x 3], interpreted to be pathogenic. We present this case report to clarify the clinical findings of a rare chromosomal anomaly, discuss the genes that may be related to the phenotype and advance the literature in terms of knowledge regarding genotypephenotype correlation.

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