Authors' objectives: The objective of this Special Report is to summarize the evidence on chromosomal microarray testing to identify CNVs in children with GDD, ID, and ASD.

Authors' recommendations: The ability to detect pathogenic CNVs underlying GDD/ID and ASD is improving. This improvement is likely due to higher CMA resolution along with increasingly extensive data concerning CNV pathogenicity and associated phenotypes and availability of those data. Professional societies have recommended CMA testing as first-line evaluation when genetic evaluation is desired as opposed to first obtaining a karyotype.3,10,20 Data supporting analytic validity are readily available only for the Affymetrix CytoScan® Dx assay, but laboratories meeting CLIA standards but using other platforms would be expected to achieve adequate technical performance. There is consistent evidence that the diagnostic yield obtained from CMA testing is higher than with karyotyping in children with GDD/ID or ASD, with or without congenital anomalies. Establishing the pathogenicity of detected CNVs relies on evidence, informatics, and genetics expertise. A particular challenge when considering the evidence and methods used to determine variant pathogenicity is that, outside the more common syndromes, diagnoses include a large number of rare disorders a clinician, even a specialist, might not encounter during a lifetime. Identifying a pathogenic variant can: (1) impact the search for a diagnosis, (2) inform follow-up that can benefit a child by reducing morbidity, and (3) affect reproductive planning for parents and potentially the affected patient. Finally, we were unable to identify case reports of incorrect diagnoses; how often they might occur is unclear. For families desiring a genetic diagnosis and what might follow from one, CMA testing can establish a diagnosis more often than other approaches such as karyotyping. Still, other assays identify genetic alterations not detected by an array. The complexities of CMA testing, interpretation, understanding its limitations, and the potential implications requires that testing is obtained by clinicians with genetic expertise, that families receive genetic counseling, and that testing be performed in laboratories meeting recommended molecular pathology standards.

Project Status: Completed

Year Published: 2015

URL for published report: http://www.bcbs.com/blueresources/tec/vols/30/30_2.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: BlueCross BlueShield Association (BCBS)