title: Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.
abstract: Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype ( approximately 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.
authors.affiliation: Division of Genetics and Department of Laboratory Medicine, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA. david.miller2@childrens.harvard.edu
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Adam
authors.forename: Swaroop
authors.initials: S
authors.lastname: Aradhya
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Biesecker
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Brothman
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Church
authors.forename: John A
authors.initials: JA
authors.lastname: Crolla
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: W Andrew
authors.initials: WA
authors.lastname: Faucett
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.forename: Jan M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Ada
authors.initials: A
authors.lastname: Hamosh
authors.forename: Laird
authors.initials: L
authors.lastname: Jackson
authors.forename: Erin B
authors.initials: EB
authors.lastname: Kaminsky
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kuhn
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: James M
authors.initials: JM
authors.lastname: Ostell
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Dimitri J
authors.initials: DJ
authors.lastname: Stavropoulos
authors.forename: James H
authors.initials: JH
authors.lastname: Tepperberg
authors.forename: Erik C
authors.initials: EC
authors.lastname: Thorland
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Darrel J
authors.initials: DJ
authors.lastname: Waggoner
authors.forename: Michael S
authors.initials: MS
authors.lastname: Watson
authors.forename: Christa Lese
authors.initials: CL
authors.lastname: Martin
authors.forename: David H
authors.initials: DH
authors.lastname: Ledbetter
mesh_terms: D002648:Child; D002871:Chromosome Banding; D025063:Chromosome Disorders / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D006801:Humans; D007621:Karyotyping
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