Yield of karyotyping in children with developmental delay and/or dysmorphic features in Sohag University Hospital, Upper Egypt

Sadek, Abdelrahim Abdrabou; Mohamed, Mostafa A.

doi:10.1016/j.ejmhg.2017.12.007

Cited by 8 publications

(13 citation statements)

References 27 publications

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“…This high diagnostic rate observed in our cohort could be due to the effective clinical triage of our ID patients and the fact that prenatal diagnoses is rarely done throughout the public health system in Brazil. Moreover, Down Syndrome (DS) was the most prevalent aneuploidy in our cohorts, consistent with several other previous observations that DS is responsible for the largest proportion of chromosomal findings reported by the karyotype [ 18 ], which has also been the leading cause of this phenotypic trait among children [ 19 – 21 ].…”

Section: Discussionsupporting

confidence: 92%

Diagnostic yield of patients with undiagnosed intellectual disability, global developmental delay and multiples congenital anomalies using karyotype, microarray analysis, whole exome sequencing from Central Brazil

et al. 2022

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Intellectual Disability (ID) is a neurodevelopmental disorder that affects approximately 3% of children and adolescents worldwide. It is a heterogeneous and multifactorial clinical condition. Several methodologies have been used to identify the genetic causes of ID and in recent years new generation sequencing techniques, such as exome sequencing, have enabled an increase in the detection of new pathogenic variants and new genes associated with ID. The aim of this study was to evaluate exome sequencing with analysis of the ID gene panel as a tool to increase the diagnostic yield of patients with ID/GDD/MCA in Central Brazil, together with karyotype and CMA tests. A retrospective cohort study was carried out with 369 patients encompassing both sexes. Karyotype analysis was performed for all patients. CMA was performed for patients who did not present structural and or numerical alterations in the karyotype. Cases that were not diagnosed after performing karyotyping and CMA were referred for exome sequencing using a gene panel for ID that included 1,252 genes. The karyotype identified chromosomal alterations in 34.7% (128/369). CMA was performed in 83 patients who had normal karyotype results resulting in a diagnostic yield of 21.7% (18/83). Exome sequencing with analysis of the ID gene panel was performed in 19 trios of families that had negative results with previous methodologies. With the ID gene panel analysis, we identified mutations in 63.1% (12/19) of the cases of which 75% (9/12) were pathogenic variants,8.3% (1/12) likely pathogenic and in 16.7% (2/12) it concerned a Variant of Uncertain Significance. With the three methodologies applied, it was possible to identify the genetic cause of ID in 42.3% (156/369) of the patients. In conclusion, our studies show the different methodologies that can be useful in diagnosing ID/GDD/MCA and that whole exome sequencing followed by gene panel analysis, when combined with clinical and laboratory screening, is an efficient diagnostic strategy.

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Section: Discussionsupporting

confidence: 92%

Diagnostic yield of patients with undiagnosed intellectual disability, global developmental delay and multiples congenital anomalies using karyotype, microarray analysis, whole exome sequencing from Central Brazil

et al. 2022

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“…Another retroprospective study by Sadek et al, 2018, on the yield of chromosomal study in children with global developmental delay and dysmorphic features demonstrated 61.1% of the sample size with abnormal karyotype [17]. Our study results were almost similar as it showed a statistically significant association between the presence of dysmorphic features and chromosomal abnormalities.…”

Section: Vol 7 | Issue 9 | September 2020supporting

confidence: 78%

“…Cytogenetic analysis performed in different populations worldwide indicates that trisomy 21 is the most common variant of Down's syndrome, with incidence varying between 83.82% and 95.51% as reported by various authors [17][18][19]. The reported occurrence of Down's syndrome in our study based on the singlecenter data was 48.6%.…”

Section: Vol 7 | Issue 9 | September 2020supporting

confidence: 59%

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Phenotypic variance in children with chromosomal aberrations – A cohort study

Abouzaid¹,

James²,

Shatla³

2020

Indian J Child Health

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C hromosomal abnormalities occur in approximately 8% of fertilized ova but only 0.6% of liveborn infants. The syndromes caused by chromosomal abnormalities include trisomy 21, trisomy 13, trisomy 18, Turner syndrome, Klinefelter syndrome, as well as chromosomal duplications, deletions, and inversions [1]. Fida et al. in 2007 reported that congenital anomalies occur in 3% of all infants worldwide including structural malformation, chromosomal abnormalities, and metabolic disorders [2]. Chromosomal abnormalities can be either inherited from a parent (e.g., translocation) or can develop spontaneously. Hence, chromosomal studies are performed on both the parents and the child with the abnormality. Advances in molecular biology and cytogenetic techniques permit the identification of many diverse types of genomic variants, which contribute to human disease, phenotypic variation, and karyotypic evolution [3]. Nearly 60% of congenital anomalies are of unknown origin. Genetic congenital anomalies, such as chromosomal abnormalities, have a vast research while those of environmental etiology caused by teratogens, are the least investigated [4]. In addition to genetic causes for congenital anomalies, factors such as infectious agents and environmental agents like radiation lead to chromosomal aberrations [5]. The maternal factors including age, lifestyle, type of pregnancy and maternal health, have also been researched and connected to the occurrence of congenital anomalies [6]. Primary prevention seeks to ensure that the individuals are born free of congenital anomalies. Services for the primary prevention of congenital malformations include basic reproductive health-care approach [7]. Cytogenetic techniques can diagnose chromosomal abnormalities and investigate the possible etiology of birth defects. It is important to know the clinical data of chromosomal abnormalities to explore the corresponding relationship between the observational characteristics of an individual resulting from the interaction of its genotype and the environment [8]. Although congenital anomalies contribute to a significant proportion of perinatal and infant morbidity and mortality, approximately 50% of them are not assigned to a specific cause [9]. However,

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“…The first step, for primary identification in cytogenetic techniques is the karyotyping which remains a precise and feasible method especially in small supernumerary marker chromosome (sSMC) (19). sSMC are detected in about 0.3% of cases with multiple congenital anomalies (MCA) and/or developmental delay (20,21). Classical karyotyping detects abnormalities in 3-15% of cases with multiple congenital malformation (22).…”

Section: Discussionmentioning

confidence: 99%

Multiplex ligation dependent probe amplification - A useful, fast and cost-effective method for identification of small supernumerary marker chromosome in children with developmental delay and congenital heart defect

Crauciuc

Tripon

Bogliș

et al. 2018

Revista Romana De Medicina De Laborator

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Small supernumerary marker chromosome (sSMC) is a rare chromosomal abnormality and is detected in about 0.3% in cases with multiple congenital anomalies (MCA) and/or developmental delay. Different techniques for investigation of cases with MCA and/or developmental delay are available ranging from karyotyping to molecular cytogenetic technique and ultimately multiplex ligation dependent probe amplification (MLPA). Here we present a patient with multiple congenital anomalies for which classical cytogenetic technique was used as a first step in diagnosis and the results being confirmed by MLPA. The karyotype disclosed a sSMC considered to be a fragment of chromosome 22. The MLPA analysis using SALSA MLPA probemix P064-C2 Microdeletion Syndromes-1B confirmed the karyotype results, and according to the manufacturer’s recommendation we performed another confirmation analysis with MLPA probemix P311-B1 Congenital Heart Disease and MLPA probemix P250-B2 DiGeorge. We also suspected an Emanuel syndrome and performed another MLPA analysis with SALSA MLPA probemix P036-E3 Subtelomeres Mix 1 and probemix P070-B3 Subtelomeres Mix 2B for investigation of subtelomeric region that revealed a duplication of 11q25 region and the confirmation was performed using SALSA MLPA probemix P286-B2 Human Telomere-11. In conclusion, we consider that MLPA is a valuable method for identification of sSMC in children with developmental delay and congenital anomalies. Genetic diagnosis using different molecular techniques, such as MLPA, for increasing accuracy in identification of chromosomal structural aberrations has an important role in clinical diagnosis and in genetic counselling and our case explain the importance of using a specific laboratory technique for each stage of diagnosis.

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Yield of karyotyping in children with developmental delay and/or dysmorphic features in Sohag University Hospital, Upper Egypt

Cited by 8 publications

References 27 publications

Diagnostic yield of patients with undiagnosed intellectual disability, global developmental delay and multiples congenital anomalies using karyotype, microarray analysis, whole exome sequencing from Central Brazil

Diagnostic yield of patients with undiagnosed intellectual disability, global developmental delay and multiples congenital anomalies using karyotype, microarray analysis, whole exome sequencing from Central Brazil

Phenotypic variance in children with chromosomal aberrations – A cohort study

Multiplex ligation dependent probe amplification - A useful, fast and cost-effective method for identification of small supernumerary marker chromosome in children with developmental delay and congenital heart defect

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