A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect

2018 ◽  
Vol 154 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Beata Aleksiūnienė ◽  
Egle Preiksaitiene ◽  
Aušra Morkūnienė ◽  
Laima Ambrozaitytė ◽  
Algirdas Utkus
Keyword(s):  
Intellectual Disability ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
De Novo ◽  
Molecular Karyotyping ◽  
Pcr Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Protein Coding ◽  
Heart Defect

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features.

Chromosomal microarray analysis in fetuses with an isolated congenital heart defect: A retrospective, nationwide, multicenter study in France

2019 ◽  
Vol 39 (6) ◽  
pp. 464-470 ◽  
Author(s):  
Marguerite Hureaux ◽  
Sarah Guterman ◽  
Bérénice Hervé ◽  
Marianne Till ◽  
Sylvie Jaillard ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Congenital Heart Defect ◽  
Multicenter Study ◽  
Congenital Heart ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Heart Defect

A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity

2015 ◽  
Vol 167 (9) ◽  
pp. 2042-2051 ◽  
Author(s):  
Vincenzo Salpietro ◽  
Martino Ruggieri ◽  
Kshitij Mankad ◽  
Gabriella Di Rosa ◽  
Francesca Granata ◽  
...  
Keyword(s):  
Congenital Heart Defect ◽  
Congenital Heart ◽  
De Novo ◽  
Growth Failure ◽  
Joint Laxity ◽  
Cerebellar Vermis ◽  
Heart Defect

scholarly journals 15q26 deletion in a patient with congenital heart defect, growth restriction and intellectual disability: case report and literature review

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Yahya Benbouchta ◽  
Nicole De Leeuw ◽  
Saadia Amasdl ◽  
Aziza Sbiti ◽  
Dominique Smeets ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Candidate Genes ◽  
Congenital Heart Defect ◽  
Cytogenetic Analysis ◽  
Congenital Heart ◽  
Clinical Manifestations ◽  
Growth Restriction ◽  
Septal Defects ◽  
Heart Defect

Abstract Background 15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations. Case presentation We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A. Conclusion We report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

scholarly journals A novel GATA6 variant in a boy with neonatal diabetes and diaphragmatic hernia: a familial case with a review of the literature

2019 ◽  
Vol 32 (9) ◽  
pp. 1027-1030 ◽  
Author(s):  
Odile Gaisl ◽  
Daniel Konrad ◽  
Pascal Joset ◽  
Mariarosaria Lang-Muritano
Keyword(s):  
Diaphragmatic Hernia ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
De Novo ◽  
Heart Defects ◽  
Neonatal Diabetes ◽  
Short Review ◽  
Review Of The Literature ◽  
Mild Phenotype ◽  
Heart Defect

Abstract GATA6 gene variants come along with possible features such as pancreas agenesis/hypoplasia, neonatal diabetes and congenital heart defect. Congenital hypothyroidism, and hepatobiliary and gut abnormalities are also detectable. Children with congenital heart defects and neonatal diabetes were already described in 1970. GATA6 variants can be due to de novo variants or due to inherited variants. To date, 11 cases due to an inherited variant have been described. Herein we present a novel heterozygous GATA6 variant (c.1291C > T p.[Gln431*]) in a boy with transient neonatal diabetes, diaphragmatic hernia, congenital heart defect and early-onset scoliosis. The same variant was also present in the mother. At the age of 3 years, a random evaluation revealed a hemoglobin A1c (HbA1c) level of 7.8% (62 mmol/mol) without any diabetes-related symptoms. He was started on insulin therapy and HbA1c normalized. A short review of the literature of hereditary cases of the GATA6 variant revealed the variable phenotypic spectrum and showed that patients with a mild phenotype are likely to have children with a more severe phenotype.

scholarly journals Chromosomal Microarray Analysis in Children with Unexplained Developmental Delay/Intellectual Disability

2018 ◽  
Vol 08 (01) ◽  
pp. 001-009
Author(s):  
Pinar Arican ◽  
Berk Ozyilmaz ◽  
Dilek Cavusoglu ◽  
Pinar Gencpinar ◽  
Kadri Erdogan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Copy Number Variants ◽  
Autism Spectrum ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Genetic Syndromes ◽  
Pathogenic Cnvs ◽  
Spectrum Disorders

AbstractChromosomal microarray (CMA) analysis for discovery of copy number variants (CNVs) is now recommended as a first-line diagnostic tool in patients with unexplained developmental delay/intellectual disability (DD/ID) and autism spectrum disorders. In this study, we present the results of CMA analysis in patients with DD/ID. Of 210 patients, pathogenic CNVs were detected in 26 (12%) and variants of uncertain clinical significance in 36 (17%) children. The diagnosis of well-recognized genetic syndromes was achieved in 12 patients. CMA analysis revealed pathogenic de novo CNVs, such as 11p13 duplication with new clinical features. Our results support the utility of CMA as a routine diagnostic test for unexplained DD/ID.

scholarly journals Molecular characterization of a complex small supernumerary marker chromosome derived from chromosome 18p: an addition to the literature

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eleonora Marchina ◽  
Michela Forti ◽  
Mariella Tonelli ◽  
Stefania Maccarini ◽  
Francesca Malvestiti ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Molecular Characterization ◽  
De Novo ◽  
Marker Chromosome ◽  
Uniparental Disomy ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Specific Syndrome ◽  
Trisomy 18P

Abstract Background Small supernumerary marker chromosomes (sSMC) are a heterogeneous group of structurally abnormal chromosomes, with an incidence of 0,044% in newborns that increases up to almost 7 times in developmentally retarded patients. sSMC from all 24 chromosome have been described, most of them originate from the group of the acrocentric, with around half deriving from the chromosome 15. Non-acrocentric sSMC are less common and, in the 30 percent of the cases, are associated with phenotypic effect. Complex sSMC consist of chromosomal material derived from more than one chromosome. Genotype–phenotype correlations in patients with sSMC are difficult to assess. Clinical features depend on factors such as its size, genetic content, the involvement of imprinted genes which may be influenced by uniparental disomy and the level of mosaicism. Trisomy of the short arm of chromosome 18 (18p) is an infrequent finding and does not appear to be associated with a specific syndrome. However, mild intellectual disability with or without other anomalies is reported in almost one-third of the patients. Case presentation Here we present clinical and molecular characterization of a new case of de novo complex sSMC consisting of the entire short arm of chromosome 18p associated with a centromere of either chromosome 13 or 21, evidenced in a 5-year-old boy during diagnostic workup for moderate intellectual disability and dysmorphisms. To date, only seven cases of isolated trisomy 18p due to a sSMC have been reported, three of which have been characterized by array CGH. In two of them the breakpoints and the size of the duplication have been described. In the manuscript we also reviewed cases reported in the DECIPHER database carrying similar duplication and also considered smaller duplications within the region of interest, in order to evaluate the presence of critical regions implicated in the pathological phenotype. Conclusions Our case provides additional information about phenotypic effects of pure trisomy 18p, confirms chromosomal microarray analysis as gold standard to characterize complex sSMC, and supplies additional elements for genetic counselling.

scholarly journals Genetic developmental disability diagnosed in adulthood: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Adam Langenfeld ◽  
Lynn Schema ◽  
Judith K. Eckerle
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Developmental Disability ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
Genetic Counselor ◽  
Functional Impairments ◽  
Heart Defect ◽  
American Patient ◽  
History Of

Abstract Background Developmental disabilities (DD) are an umbrella term for conditions associated with functional impairments in physical, learning, language, or behavior areas. Intellectual disability (ID) is a type of developmental disability that results in delays in cognitive or intellectual functioning, such as reasoning, learning, and problem-solving, and adaptive behaviors including social and practical life skills. DD can be due to a variety of factors, ranging from environmental exposures to genetic mutations, and studies suggest that up to 40% of DDs may be caused by genetic issues. Case presentation In this case study, we present an 18-year-old internationally adopted female Chinese American patient with a known history of developmental delay, intellectual disability, strabismus, and a congenital heart defect who had not been tested for genetic causes of her delay prior to presentation. When evaluated with chromosomal microarray, the patient demonstrated a deletion on the short arm of chromosome 5, an area associated with Cri-du-chat syndrome. This chromosomal deletion was a likely explanation for her history of developmental delays, intellectual disability, and congenital heart defect, in addition to her history of institutionalization and the trauma of multiple caregiver transitions in early childhood. The patient was referred for further evaluation by a geneticist and genetic counselor. Conclusions This case highlights that the underlying cause of developmental delay is often multifactorial, and underscores the importance of a full medical evaluation, including genetic testing, for children with intellectual disability. Using this approach, healthcare professionals can identify potential diagnoses and provide more targeted resources to families.

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