Appropriateness of array‐CGH in the ADHD clinics: A comparative study

Abstract

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorder with a worldwide prevalence of about 5%. The disorder is characterized by inattentive, hyperactive and impulsive behavior and is often comorbid with other neuropsychiatric conditions. Array comparative genomic hybridization (array‐CGH) testing has been proved to be useful to detect chromosomal aberrations in several neuropsychiatric conditions including autism spectrum disorders (ASD) and intellectual disability (ID). The usefulness of array‐CGH in the ADHD clinics is still debated and no conclusive evidence has been reached to date. We performed array‐CGH in 98 children and adolescents divided in two similarly sized groups according to the clinical diagnosis: (a) one group diagnosed with ADHD as primary diagnosis; (b) the other group in which ADHD was co‐morbid with ASD and/or ID. We detected pathogenetic and likely pathogenetic copy number variants (CNVs) in 12% subjects in which ADHD was co‐morbid with autism and/or intellectual disability and in 8.5% subjects diagnosed with ADHD as primary diagnosis. Detection of CNVs of unknown clinical significance was similar in the two groups being 27% and 32%, respectively. Benign and likely benign CNVs accounted for 61% and 59.5% in the first and second group, respectively. Differences in the diagnostic yield were not statistically significant between the two groups (P > .05). Our data strongly suggest that array‐CGH (a) is a valuable diagnostic tool to detect clinically significant CNVs in individuals with ADHD even in the absence of comorbidity with ASD and/or ID and (b) should be implemented routinely in the ADHD clinics.

Yield of array‐CGH analysis in Tunisian children with autism spectrum disorder

“…Depending on array model and platform, array comparative genomic hybridization (aCGH) allows identifying the presence of CNVs (deletions and duplications) at the whole genome level with a resolution down to just ~5-100 Kb. Hence aCGH, as already extensively described in the literature, has been confirmed as a "gold standard" first-level test in the genetic diagnosis of ASD (Aradhya et al, 2007;Miller et al, 2010;Sanders et al, 2015) and for neurodevelopmental disorders in general (Baccarin et al, 2020). Much evidence revealed that copy number variants (CNVs) detected by aCGH are major contributors to ASD pathogenesis in up to 10%-15% of affected children (Miller et al, 2010;Sebat et al, 2007).…”

“…Autism spectrum disorder (ASD) encompasses a group of neurodevelopmental disorders (the "autisms") characterized by impairment in social interaction and communication, including deficits in social reciprocity, accompanied by restricted interests, repetitive patterns of behavior, and abnormal sensory processing (American Psychiatric Association, 1994;Persico et al, 2020). Its prevalence rates range from 1/54 children and 1/45 adults in the United States (Dietz et al, 2020;Maenner et al, 2020), to 1/87 children in Italy and 1/102 adults in England (Brugha et al, 2011;Narzisi et al, 2018).…”

“…ASD has strong genetic underpinnings. Familial recurrence rates are approximately 15%-25% for male and 5%-15% for female offspring (Ozonoff et al, 2011;Persico et al, 2020), much higher than population rates (Brugha et al, 2011;Dietz et al, 2020;Maenner et al, 2020;Narzisi et al, 2018). Twin studies have revealed that heritability can range from 38% to 90%, with approximately 50% as the most likely estimate (Huguet et al, 2016).…”

Catecholaminergic and Cholinergic Neuromodulation in Autism Spectrum Disorder: A Comparison to Attention-Deficit Hyperactivity Disorder

“…Specifically, CHRNA7 (coding the α7-nAChR (Jensen et al 2005)), has been associated with ASD, as has been CHRFAM7A (Bacchelli et al 2015) -an exclusively human and highly polymorphic hybrid gene consisting of a duplicated portion of CHRNA7 fused to exons A-E of FAM7A (Gault et al 1998;Wall et al 2009;Pinto et al 2010;Casey et al 2012;Huguet et al 2013;Bacchelli et al 2015;Gillentine and Schaaf 2015;Gillentine et al 2017). CHRNA7 has also been implicated in ADHD (Baccarin et al 2020;Gillentine et al 2017;Gillentine and Schaaf 2015;Sinkus et al 2015;Valbonesi et al 2015), but not all studies have not replicated this finding (Kent et al 2001;Faraone et al 2005;Ross 2012).…”

“…CHRFAM7A has also been associated with ADHD (Baccarin et al 2020;Williams et al 2012), but replication is required to confirm this association. Another gene, CHRNA4, codes for the α4-nAChR and has been identified as a candidate gene for ASD, but this gene seems to only play a role in specific cases (i.e.…”