Chromosomal Microarray Analysis Has a Poor Diagnostic Yield in Children with Developmental Delay/Intellectual Disability
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ORIGINAL ARTICLE
Chromosomal Microarray Analysis Has a Poor Diagnostic Yield in Children with Developmental Delay/Intellectual Disability When Concurrent Cerebellar Anomalies Are Present Claudia Ciaccio 1
&
Chiara Pantaleoni 1 & Sara Bulgheroni 1 & Francesca Sciacca 2 & Stefano D’Arrigo 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Chromosomal microarray analysis is commonly used as screening test for children with neurodevelopmental issues, also in case of complex neurological phenotypes. Developmental delay/intellectual disability is a common presentation sign in pediatric ataxias, diseases with high clinical and genetic heterogeneity. In order to determine the diagnostic yield of Array-CGH in such conditions, all the tests performed in the last 10-year activity of a single referral center in children who present, besides the neurodevelopmental impairment, cerebellar abnormalities have been systematically gathered. The study demonstrates that, except for Dandy-Walker malformation or poly-malformative phenotypes, chromosomal microarray analysis should be discouraged as first-line diagnostic test in pediatric ataxias with neurodevelopmental disability. Keywords Array-CGH . Pediatric ataxia . Developmental delay . Intellectual disability . Cerebellar anomalies
Introduction Chromosomal microarray analysis (CMA) is routinely used as first-line diagnostic test for children presenting with developmental delay (DD) or intellectual disability (ID). Since its spread to clinical practice, the high diagnostic yield of this technique in cognitive impairment has been confirmed by several studies and by Centers of different Countries worldwide [1–6], thus offering an estimation of its yield that reflects the prevalence of pathogenic copy number variants (CNVs) in diverse ethnic groups. Such prevalence is reported in a range that varies from the 13–14% of older works [1, 7] to a higher value, 21% and up to 28%, of more recent studies [3, 6], consistent with the increasing resolution and accuracy of the test with ages.
* Claudia Ciaccio [email protected] 1
Developmental Neurology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy
2
Department of Diagnostic and Technology, Laboratory of Cytogenetic, Unit of Neurological Biochemistry and Neuropharmacology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
The likelihood of detecting a chromosomal unbalance rises with the severity of the impairment [1, 2] and in the presence of additional signs and symptoms, such as further neurodevelopmental or neurologic issues (mostly autism spectrum disorder, epilepsy, and infantile hypotonia), facial dysmorphisms, and congenital malformations [2, 3, 8]. The evidence of this benefit led in 2010 to the publication of a consensus statement where chromosomal microarray has been recommended as first-tier analysis for all individuals with developmental disabilities or congenital anomalies [9]. Following this and given its progres
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