Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

David T. Miller, Margaret P. Adam, Swaroop Aradhya, Leslie G. Biesecker, Arthur R. Brothman, Nigel P. Carter, Deanna M. Church, John A. Crolla, Evan E. Eichler, Charles J. Epstein, W. Andrew Faucett, Lars Feuk, Jan M. Friedman, Ada Hamosh, Laird Jackson, Erin B. Kaminsky, Klaas Kok, Ian D. Krantz, Robert M. Kuhn, Charles LeeJames M. Ostell, Carla Rosenberg, Stephen W. Scherer, Nancy B. Spinner, Dimitri J. Stavropoulos, James H. Tepperberg, Erik C. Thorland, Joris R. Vermeesch, Darrel J. Waggoner, Michael S. Watson, Christa Lese Martin, David H. Ledbetter

Research output: Contribution to journalArticlepeer-review

1580 Scopus citations

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 (∼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.

Original languageEnglish (US)
Pages (from-to)749-764
Number of pages16
JournalAmerican journal of human genetics
Volume86
Issue number5
DOIs
StatePublished - May 14 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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