Original ArticleMicroarray Analysis in Children With Developmental Disorder or Epilepsy
Introduction
Chromosomal microarray analysis is a technique that identifies genetic imbalances, such as supernumerary markers and areas of loss of heterozygosity [1]. Its diagnostic role in pediatric neurology is still evolving, and is mainly focused on revealing the etiologies of developmental delay and autism. This cytogenetic technique has become an important tool in the detection of small chromosomal abnormalities involving copy number variations. It has the potential to identify chromosomal imbalances associated with mental retardation and multiple congenital anomalies [2]. Few studies have investigated the role of chromosomal microarray analysis in the etiologic diagnosis of patients with epilepsy. Some studies revealed an association between chromosomal copy number variation and epilepsy. Kim et al. [3], in their series of 60 children with epilepsy, reported that the most frequent abnormality in children with epilepsy was a gain in copy number variation. The objective of this study was to describe our experience of using chromosomal microarray analysis at our institution.
Section snippets
Patients and Methods
We retrospectively reviewed the charts of 82 patients with neurodevelopmental disorders who were referred to our Section of Neurology for epilepsy, speech delay, motor impairment, or autism between January 2006 and June 2009. All the children had undergone chromosomal analysis, and were screened for other chromosomal abnormalities using chromosomal microarray analysis. Several clinical variables were collected: the presence of mental retardation or developmental delay, autism, learning
Results
We studied 82 children (mean age ± S.D., 5.7 ± 5 years), including 45 (55%) boys and 37 (45%) girls. All patients in the study manifested a normal karyotype. Chromosomal microarray produced abnormal results in 17 (21%). Three additional children demonstrated increased homozygosity, suggesting uniparental disomy. Therefore, the total number of abnormal results was 20 (23.5%). Deletions comprised 74% of all abnormalities, most commonly in chromosome 7 (n = 4).
Two children exhibited chromosomal
Discussion
Chromosomal microarray is a cytogenetic technique that can identify copy number variations in patients whose karyotype screening produced normal results [4], [5]. The diagnostic use of chromosomal microarray in children with developmental delays, mental retardation, and epilepsy is still evolving. Our results indicate that single nucleotide polymorphisms and bacteria artificial chromosome based comparative genomic hybridization microarray techniques can function as important components in
References (13)
- et al.
Altered DNA copy number in patients with different seizure disorder type: By array-CGH
Brain Dev
(2007) American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation
Genet Med
(2005)- et al.
Application of array-based comparative genome hybridization in children with developmental delay or mental retardation
Pediatr Neonatol
(2008) - et al.
Determination of genomic breakpoints in an epileptic patient using genotyping array
Biochem Biophys Res Commun
(2006) - et al.
Detection of chromosomal imbalances in children with idiopathic mental retardation by array based comparative genomic hybridisation (array-CGH)
J Med Genet
(2005) - et al.
Clinical utility of array CGH for the detection of chromosomal imbalances associated with mental retardation and multiple congenital anomalies
Ann NY Acad Sci
(2009)
Cited by (19)
Clinical utility of genetic testing in pediatric drug-resistant epilepsy: A pilot study
2014, Epilepsy and BehaviorCitation Excerpt :Developmental delay was found in 78% of our patients, which was more than what has been reported in studies [34]. Prior studies have found that genetic diagnoses are often associated with generalized epilepsy and EE [35,36]. We found that these two factors were associated with positive genetic test results, but the numbers were too small to draw any definitive conclusions if these factors were associated with diagnostic test results: there was only a trend for generalized epilepsy to be associated with diagnostic results, and this trend did not achieve statistical significance.
Fraternal twins with autism, severe cognitive deficit, and epilepsy: Diagnostic role of chromosomal microarray analysis
2014, Seminars in Pediatric NeurologyCitation Excerpt :The frequency of disease-causing copy number variants has been described in 20%-25% of children with moderate to severe intellectual disability accompanied by malformations or dysmorphic features and in 5%-10% of cases of autism.3 It is therefore increasingly used as a first-line test in the diagnostic workup or children with autism, especially if associated with other problems such as congenital malformations, dysmorphic features, developmental delay, cognitive impairment, behavioral abnormalities, or epilepsy.4-6 Our cases, diagnosed with chromosomal microarray analysis, expand the phenotype of NRXN mutations and corroborate the important role of NRXN1 in autism and intellectual disability.
A genetic diagnostic approach to infantile epileptic encephalopathies
2012, Journal of Clinical NeuroscienceCitation Excerpt :These techniques will detect relatively common and recognizable microdeletion syndromes such as 1p36 microdeletion syndrome and Wolf–Hirschhorn syndrome as well as novel copy number changes. Various studies examining detection of aCGH anomalies in epilepsy cohorts have reported specific susceptilibity loci (15q13.3, 16p13.11, and 15q11.2) with an incidence of 1% but these are clinically heterogeneous for age of onset, severity, and association with other neuropsychiatric symptoms such as autism and schizophrenia.31,34 Table 4 lists recently described non-syndromic monogenic causes of epileptic encephalopathy.
Comorbidities associated with genetic abnormalities in children with intellectual disability
2021, Scientific ReportsParoxysmal Movement Disorders
2021, Frontiers in NeurologyA novel interstitial deletion of chromosome 2q21.1-q23.3: Case report and literature review
2020, Molecular Genetics and Genomic Medicine