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

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.

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

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.

Constitutional de novo deletion CNV encompassing REST predisposes to diffuse hyperplastic perilobar nephroblastomatosis (HPLN)

2020 ◽  
pp. jmedgenet-2020-107087
Author(s):  
Zerin Hyder ◽  
Adele Fairclough ◽  
Mike Groom ◽  
Joan Getty ◽  
Elizabeth Alexander ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Cancer Predisposition ◽  
Tumour Suppressor ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Predisposition Genes ◽  
Work Up

BackgroundNephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such as WT1, REST and TRIM28 have been described in apparently isolated (non-familial) WT.Despite constitutional CNVs being a well-studied cause of developmental disorders, their role in cancer predisposition is less well defined, so that the interpretation of cancer risks associated with specific CNVs can be complex.ObjectiveTo highlight the role of a constitutional deletion CNV (delCNV) encompassing the REST tumour suppressor gene in diffuse hyperplastic perilobar nephroblastomatosis (HPLN).Methods/resultsArray comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330–57,947,405)x1. The REST tumour suppressor gene is located at GRCh37 chr4:57,774,042–57,802,010.ConclusionThis delCNV encompassing REST is associated with nephroblastomatosis. Deletion studies should be included in the molecular work-up of inherited predisposition to WT/nephroblastomatosis. Detection of delCNVs involving known cancer predisposition genes can yield insights into the relationship between underlying genomic architecture and associated tumour risk.

scholarly journals Identification of an Identical de Novo SCAMP5 Missense Variant in Four Unrelated Patients With Seizures and Severe Neurodevelopmental Delay

2020 ◽  
Vol 11 ◽  
Author(s):  
Xianru Jiao ◽  
Manuela Morleo ◽  
Vincenzo Nigro ◽  
Annalaura Torella ◽  
Stefano D’Arrigo ◽  
...  
Keyword(s):  
Language Development ◽  
Developmental Disorders ◽  
De Novo ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Autism Spectrum ◽  
Neurodevelopmental Delay ◽  
Dysmorphic Features ◽  
Severe Intellectual Disability ◽  
Neurological Exam

Objective: To establish and broaden the phenotypic spectrum of secretory carrier membrane protein (SCAMP5) associated with epilepsy and neurodevelopmental delay.Methods: A Chinese patient was identified at the First Hospital of Peking University, and the three unrelated patients were recruited from two different countries (Italy and United States) through GeneMatcher. SCAMP5 pathogenic variants were identified by whole exome sequencing; clinical data of the patients were retrospectively collected and analyzed.Result: The onset age of seizures was ranged from 6 to 15 months. Patients had different types of seizures, including focal seizures, generalized tonic-clonic seizures and tonic seizure. One patient showed typical autism spectrum disorder (ASD) symptoms. Electroencephalogram (EEG) findings presented as focal or multifocal discharges, sometimes spreading to generalization. Brain magnetic resonance imaging (MRI) abnormalities were present in each patient. Severe intellectual disability and language and motor developmental disorders were found in our patients, with all patients having poor language development and were nonverbal at last follow-up. All but one of the patients could walk independently in childhood, but the ability to walk independently in one patient had deteriorated with age. All patients had abnormal neurological exam findings, mostly signs of extrapyramidal system involvement. Dysmorphic features were found in 2/4 patients, mainly in the face and trunk. All four unrelated patients were found to have the same heterozygous pathogenic SCAMP5 de novo variant (p. Gly180Trp).Conclusion: Epilepsy, severe developmental delay, abnormal neurological exam findings, with or without ASD or variably dysmorphic features and were common in patients with SCAMP5 variant. The onset time and type of seizure varied greatly. The EEG and brain MRI findings were not consistent, but diverse and nonspecific. The motor ability of patients with heterozygous SCAMP5 variant might have a regressive course; language development was more severely affected.

scholarly journals A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 707 ◽  
Author(s):  
Orazio Palumbo ◽  
Pietro Palumbo ◽  
Ester Di Muro ◽  
Luigia Cinque ◽  
Antonio Petracca ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Chromosome Region ◽  
Snp Array ◽  
Supporting Evidence ◽  
Speech Delay ◽  
Dysmorphic Features ◽  
Phenotype Comparison ◽  
Molecular Comparison ◽  
Snp Array Analysis

No data on interstitial microduplications of the 16q24.2q24.3 chromosome region are available in the medical literature and remain extraordinarily rare in public databases. Here, we describe a boy with a de novo 16q24.2q24.3 microduplication at the Single Nucleotide Polymorphism (SNP)-array analysis spanning ~2.2 Mb and encompassing 38 genes. The patient showed mild-to-moderate intellectual disability, speech delay and mild dysmorphic features. In DECIPHER, we found six individuals carrying a “pure” overlapping microduplication. Although available data are very limited, genomic and phenotype comparison of our and previously annotated patients suggested a potential clinical relevance for 16q24.2q24.3 microduplication with a variable and not (yet) recognizable phenotype predominantly affecting cognition. Comparing the cytogenomic data of available individuals allowed us to delineate the smallest region of overlap involving 14 genes. Accordingly, we propose ANKRD11, CDH15, and CTU2 as candidate genes for explaining the related neurodevelopmental manifestations shared by these patients. To the best of our knowledge, this is the first time that a clinical and molecular comparison among patients with overlapping 16q24.2q24.3 microduplication has been done. This study broadens our knowledge of the phenotypic consequences of 16q24.2q24.3 microduplication, providing supporting evidence of an emerging syndrome.

De novo 6.9 Mb interstitial deletion on chromosome 4q31.1-q32.1 in a girl with severe speech delay and dysmorphic features

2012 ◽  
Vol 158A (4) ◽  
pp. 882-887 ◽  
Author(s):  
Antonella Fabretto ◽  
Maria Santa Rocca ◽  
Maria Dolores Perrone ◽  
Aldo Skabar ◽  
Vanna Pecile ◽  
...  
Keyword(s):  
De Novo ◽  
Interstitial Deletion ◽  
Speech Delay ◽  
Dysmorphic Features

scholarly journals A novel de novo paracentric inversion [inv(20)(q13.1q13.3)] accompanied by an 11q14.3-q21 microdeletion in a pediatric patient with an intellectual disability

2018 ◽  
Vol 21 (2) ◽  
pp. 63-67
Author(s):  
S Zachaki ◽  
E Kouvidi ◽  
A Mitrakos ◽  
L Lazaros ◽  
A Pantou ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Comparative Genomic Hybridization ◽  
Array Comparative Genomic Hybridization ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Mendelian Inheritance ◽  
Paracentric Inversion ◽  
Comparative Genomic ◽  
Published Data ◽  
Genomic Hybridization

Abstract A novel de novo paracentric inversion of the long arm of chromosome 20 [inv(20)(q13.1q13.3)], detected by conventional karyotyping in a 14-year-old boy with mental retardation is described. Further investigation by array comparative genomic hybridization (aCGH) revealed that the 20q inversion was not accompanied by microdeletions/microduplications containing disease-associated genes near or at the breakpoints. Two deletions at chromosomal regions 11q14.3q21 and 20q12 of 4.5 and 1.97 Mb size, respectively, containing important online Mendelian inheritance in man (OMIM) genes, were detected. The 4.5Mb 11q14.3q21 microdeletion was contained within a region that is involved, in most of the reported cases, with the interstitial 11q deletion and may be related to the mental retardation and developmental delay present in the patient. On the other hand, the published data about the 20q12 microdeletion are very few and it is not possible to correlate this finding with our patient’s phenotype. This case report contributes to the description of a new chromosomal entity, not previously reported, and is therefore important, especially in prenatal diagnosis and management of patients. Array comparative genomic hybridization has proven a useful technique for detecting submicroscopic rearrangements and should be offered prenatally, especially in cases of de novo karyotypically balanced chromosomal inversions or translocations in order to unveil other unbalanced chromosomal abnormalities such as deletions and amplifications.

Static Leukoencephalopathy Associated with 17p13.3 Microdeletion Syndrome: A Case Report

2019 ◽  
Vol 50 (06) ◽  
pp. 387-390 ◽  
Author(s):  
Ayaka Hirasawa-Inoue ◽  
Eri Takeshita ◽  
Yuko Shimizu-Motohashi ◽  
Akihiko Ishiyama ◽  
Takashi Saito ◽  
...  
Keyword(s):  
White Matter ◽  
Chromosomal Abnormalities ◽  
Magnetic Resonance Images ◽  
Cerebral White Matter ◽  
Comparative Genomic ◽  
White Matter Abnormality ◽  
Microdeletion Syndrome ◽  
Chromosomal Imbalance ◽  
Dysmorphic Features ◽  
Serial Brain

Background Leukoencephalopathy associated with dysmorphic features may be attributed to chromosomal abnormalities such as 17p13.3 microdeletion syndrome. Case A 19-year-old female patient was referred to our hospital for diagnostic evaluation of her leukoencephalopathy. She demonstrated moderate intellectual disability, minor dysmorphic features, and short stature. Serial brain magnetic resonance images obtained within a 16-year interval revealed prolonged T2 signals in the deep cerebral white matter with enlarged Virchow–Robin spaces. A nonsymptomatic atlas anomaly was also noted. Using microarray-based comparative genomic hybridization, we identified a 2.2-Mb terminal deletion at 17p13.3, encompassing YWHAE, CRK, and RTN4RL1 but not PAFAH1B1. Conclusion Except for atlas anomaly, the patient's clinical and imaging findings were compatible with the diagnosis of 17p13.3 microdeletion syndrome. The white matter abnormality was static and nonprogressive. The association between the atlas abnormality and this deletion remains elusive. We note the importance of exploring submicroscopic chromosomal imbalance when patients show prominent but static white matter abnormalities with discrepantly mild and stable neurological signs.

scholarly journals First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly

2021 ◽  
pp. 1-5
Author(s):  
Ayberk Turkyilmaz ◽  
Erdal Kurnaz ◽  
Atilla Cayir
Keyword(s):  
Intellectual Disability ◽  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic And Environmental Factors

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (<i>GPR120</i>, <i>KIF11</i>, <i>EXOC6</i>, <i>CYP26A1</i>, <i>CYP26C1</i>, and <i>LGI1</i>) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

Atypical Fetal Hydantoin Syndrome

PEDIATRICS ◽  
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.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Shirley Lo-A-Njoe ◽  
Lars T. van der Veken ◽  
Clementien Vermont ◽  
Louise Rafael-Croes ◽  
Vincent Keizer ◽  
...  
Keyword(s):  
Congenital Heart ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Short Life ◽  
Cardiac Anomalies ◽  
Chromosome 1Q ◽  
Dysmorphic Features ◽  
Postnatal Diagnosis ◽  
Short Life Expectancy ◽  
Mosaic Trisomy

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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