Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.
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.
Miller
David T
DT
Division of Genetics and Department of Laboratory Medicine, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA. david.miller2@childrens.harvard.edu
Adam
Margaret P
MP
Aradhya
Swaroop
S
Biesecker
Leslie G
LG
Brothman
Arthur R
AR
Carter
Nigel P
NP
Church
Deanna M
DM
Crolla
John A
JA
Eichler
Evan E
EE
Epstein
Charles J
CJ
Faucett
W Andrew
WA
Feuk
Lars
L
Friedman
Jan M
JM
Hamosh
Ada
A
Jackson
Laird
L
Kaminsky
Erin B
EB
Kok
Klaas
K
Krantz
Ian D
ID
Kuhn
Robert M
RM
Lee
Charles
C
Ostell
James M
JM
Rosenberg
Carla
C
Scherer
Stephen W
SW
Spinner
Nancy B
NB
Stavropoulos
Dimitri J
DJ
Tepperberg
James H
JH
Thorland
Erik C
EC
Vermeesch
Joris R
JR
Waggoner
Darrel J
DJ
Watson
Michael S
MS
Martin
Christa Lese
CL
Ledbetter
David H
DH
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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