scholarly journals 15q26 Deletion in a Patient with Congenital Heart Defect, Growth Restriction and Intellectual Disability: Case Report and Literature Review

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Nicole de Leeuw ◽  
Saadia Amasdl ◽  
Aziza Sbiti ◽  
Dominique Smeets ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Septal Defects ◽  
Aortic Arch Anomaly ◽  
Divergent Strabismus ◽  
Heart Defect

Abstract Background 15q26 deletion is a relatively rare chromosomal disorder described in only few cases. Patients with this aberration display numerous symptoms particularly, pre- and postnatal growth restriction, microcephaly, intellectual disability, dysmorphic gestalt and various congenital malformations. Case presentation We report on a girl, four years old, of consanguineous parents, with a de novo 15q26 deletion. Clinical manifestations included failure to thrive, 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 a left-to-right shunt, two atrial septal defects, enlarging the right heart cavities. Routine cytogenetic analysis revealed a shortened 15 chromosome with an abnormally short ened long (q) arm. Subsequent array analysis disclosed a terminal 9.15 Mb deletions detected in band 15q26.1-q26.3. Five candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, MEF2A, MCTP2, and CHD2.Conclusion 15q26 monosomy should be considered when growth retardation is associated with ear anomaly, clinodactyly and/or abnormal toe, heart defect mainly atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

scholarly journals 15q26 Deletion in a Patient with Congenital Heart Defect, Growth Restriction and Intellectual Disability: Case Report and Literature Review

2020 ◽  
Author(s):  
Yahya BENBOUCHTA ◽  
Nicole de Leeuw ◽  
Saadia Amasdl ◽  
Aziza Sbiti ◽  
Dominique Smeets ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Aortic Arch Anomaly ◽  
Divergent Strabismus ◽  
Heart Defect ◽  
Defect Growth

Abstract Background 15q26 deletion is a relatively rare chromosomal disorder described in only few cases. Patients with this aberration display numerous symptoms particularly pre- and postnatal growth restriction, microcephaly, intellectual disability, dysmorphic gestalt, and various congenital malformations. Case presentation We report on a girl, four years old, of consanguineous parents, with a de novo 15q26 deletion. Clinical manifestations included failure to thrive, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits, protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, right foot varus equine, and left club foot. Additionally, she had teething delay and divergent strabismus. Further clinical investigations showed right-to-left atrial shunting, and enlarged right heart. Routine cytogenetic analysis revealed a derivative 15 chromosome with an abnormally short long (q) arm. Subsequent array analysis disclosed a terminal 9.15 Mb deletion detected in band 15q26.1q26.3. Five candidate genes causing the phenotype were within the deleted region, i.e. IGF1R, NR2F2, MEF2A, MCTP2, and CHD2. Conclusion 15q26 monosomy should be considered when growth retardation is associated with ear anomaly, clinodactyly and/or abnormal toe, heart defect mainly atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

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 de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A Case Report and Literature Review

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yanyan Nie ◽  
Yu Mu ◽  
Jie Zheng ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mental Disorders ◽  
De Novo ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Whole Exome ◽  
De Novo Variant

Abstract Background：The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by mutation. We reported a Chinese male newborn with a de novo variant in CASK gene. Case presentation：We present an 18-day-old baby with intellectual disability and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense mutation c.764G>A of CASK gene. The mutation changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.Conclusions：In this paper, a de novo mutation of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported.CASK mutations cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.

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.

scholarly journals De novo mutations in FBRSL1 cause a novel recognizable malformation and intellectual disability syndrome

2020 ◽  
Vol 139 (11) ◽  
pp. 1363-1379
Author(s):  
Roser Ufartes ◽  
Hanna Berger ◽  
Katharina Till ◽  
Gabriela Salinas ◽  
Marc Sturm ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Xenopus Laevis ◽  
Cellular Localization ◽  
De Novo ◽  
Postnatal Growth ◽  
Global Developmental Delay ◽  
De Novo Mutations ◽  
Protein Coding ◽  
Aberrant Phenotype ◽  
Craniofacial Defects

Abstract We report truncating de novo variants in specific exons of FBRSL1 in three unrelated children with an overlapping syndromic phenotype with respiratory insufficiency, postnatal growth restriction, microcephaly, global developmental delay and other malformations. The function of FBRSL1 is largely unknown. Interestingly, mutations in the FBRSL1 paralogue AUTS2 lead to an intellectual disability syndrome (AUTS2 syndrome). We determined human FBRSL1 transcripts and describe protein-coding forms by Western blot analysis as well as the cellular localization by immunocytochemistry stainings. All detected mutations affect the two short N-terminal isoforms, which show a ubiquitous expression in fetal tissues. Next, we performed a Fbrsl1 knockdown in Xenopus laevis embryos to explore the role of Fbrsl1 during development and detected craniofacial abnormalities and a disturbance in neurite outgrowth. The aberrant phenotype in Xenopus laevis embryos could be rescued with a human N-terminal isoform, while the long isoform and the N-terminal isoform containing the mutation p.Gln163* isolated from a patient could not rescue the craniofacial defects caused by Fbrsl1 depletion. Based on these data, we propose that the disruption of the validated N-terminal isoforms of FBRSL1 at critical timepoints during embryogenesis leads to a hitherto undescribed complex neurodevelopmental syndrome.

scholarly journals De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive

2016 ◽  
Vol 99 (3) ◽  
pp. 720-727 ◽  
Author(s):  
Mari J. Tokita ◽  
Alicia A. Braxton ◽  
Yunru Shao ◽  
Andrea M. Lewis ◽  
Marie Vincent ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Congenital Malformations ◽  
De Novo ◽  
Failure To Thrive

Prenatal clinical manifestations in individuals with COL4A1/2 variants

2020 ◽  
pp. jmedgenet-2020-106896 ◽  
Author(s):  
Toshiyuki Itai ◽  
Satoko Miyatake ◽  
Masataka Taguri ◽  
Fumihito Nozaki ◽  
Masayasu Ohta ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Cerebrovascular Diseases ◽  
Growth Restriction ◽  
Foetal Growth ◽  
Type Iv ◽  
Pathogenic Variants ◽  
Gene Testing ◽  
Foetal Growth Restriction ◽  
Walker Malformation

BackgroundVariants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear.MethodsWe examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.ResultsPathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.ConclusionsPrenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.

scholarly journals A familial case of CAMK2B mutation with variable expressivity

2021 ◽  
Vol 9 ◽  
pp. 2050313X2199098
Author(s):  
Paige Heiman ◽  
Sarah Drewes ◽  
Lina Ghaloul-Gonzalez
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Clinical Manifestations ◽  
Cerebellar Atrophy ◽  
Global Developmental Delay ◽  
De Novo Mutations ◽  
Phenotypic Spectrum ◽  
Behavioral Abnormalities ◽  
Intrafamilial Variability

Variants in CAMK2-associated genes have recently been implicated in neurodevelopmental disorders and intellectual disability. The clinical manifestations reported in patients with mutations in these genes include intellectual disability (ranging from mild to severe), global developmental delay, seizures, delayed speech, behavioral abnormalities, hypotonia, episodic ataxia, progressive cerebellar atrophy, visual impairments, and gastrointestinal issues. Phenotypic heterogeneity has been postulated. We present a child with neurodevelopmental disorder caused by a pathogenic CAMK2B variant inherited from a healthy mother. A more mildly affected sib was determined to have the same variant. Monoallelic mutations in CAMK2B in patients have previously only been reported as de novo mutations. This report adds to the clinical phenotypic spectrum of the disease and demonstrates intrafamilial variability of expression of a CAMK2B mutation.

scholarly journals Clinical Manifestations in a Girl with NAA10-Related Syndrome and Genotype–Phenotype Correlation in Females

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 900
Author(s):  
Ilenia Maini ◽  
Stefano G. Caraffi ◽  
Francesca Peluso ◽  
Lara Valeri ◽  
Davide Nicoli ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Growth Failure ◽  
Autistic Traits ◽  
Missense Variant ◽  
Postnatal Growth ◽  
Young Female ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Clinical Description

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 [NM_003491:c.247C > T, p.(Arg83Cys)] variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype–phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could have relevant consequences for the clinical management of known and newly identified individuals.

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