25189 Chromosomal Microarray, Congenital, Blood (CMACB)

​​aCGH, Array CGH, Array Comparative Genomic Hybridization, Oligonucleotide Array, Oligo Array, Single Nucleotide Polymorphism (SNP) Array, Whole Genome Array, Microarray, Molecular Karyotype, CytoScan, Congenital Array, Constitutional Array, Absence of Heterozygosity (AOH), Accel

This test requires 2 blood specimens: 1 sodium heparin and 1 EDTA.

A whole blood EDTA AND a whole blood sodium heparin specimen, as well as the reason for referral, are required.

Chromosomal Microarray Patient Information

Invert collection tubes several times to mix blood.

Send whole blood and cord blood specimens in original tubes. Do not aliquot.

This test is not approved by the US Food and Drug Administration, and it is best used as an adjunct to existing clinical and pathologic information.

Chromosomal microarray data alone does not provide information about the structural nature of an imbalance.

This test does not detect balanced chromosome rearrangements such as Robertsonian or other reciprocal translocations, inversions, or balanced insertions.

This test does not detect all types and instances of uniparental disomy.

This test is not designed to detect mosaicism, although it can be detected in some cases.

This test does not detect point alterations, small deletions or insertions below the resolution of this assay, or other types of variants such as epigenetic changes.

The results of this test may reveal incidental findings not related to the original reason for referral. In such cases, studies of additional family members may be required to help interpret the results.

Families benefit from hearing genetic information multiple times and in multiple ways. A referral to a clinical genetics professional is appropriate for individuals and families to discuss the results of chromosomal microarray testing.

Interfering factors:

-Use of an improper anticoagulant (EDTA is best) or improperly mixing the blood with the anticoagulant

-Excessive transport time

-Inadequate amount of blood

-Improper packaging may result in broken, leaky, and contaminated specimen during transport

​Aneuploidy or unbalanced chromosome rearrangements are often found in patients with intellectual disability, developmental delay, autism, dysmorphic features, or congenital anomalies. Some chromosomal abnormalities are large enough to be detected with conventional chromosome analysis. However, many pathogenic rearrangements are below the resolution limits of chromosome analysis (approximately 5 megabases). Chromosomal microarray (CMA) is a high-resolution method for detecting copy number changes (gains or losses) across the entire genome in a single assay and is sometimes called a molecular karyotype.

This CMA test utilizes greater than 2 million copy number probes and approximately 750,000 single nucleotide polymorphism probes for the detection of copy number changes and regions of excessive homozygosity. Identification of regions of excessive homozygosity on a single chromosome could suggest uniparental disomy (UPD), which may warrant further clinical investigation when observed on chromosomes with known imprinting disorders associated with UPD. In addition, the detection of excessive homozygosity on multiple chromosomes may suggest consanguinity and, therefore, could be useful in determining candidate genes for further testing for autosomal recessive disorders.

An online research opportunity called GenomeConnect (genomeconnect.org) is available for the recipients of genetic test results. This patient registry collects deidentified genetic and health information to advance knowledge of genetic variants. For more information see GenomeConnect Patient Portal.

Copy number variation is found in all individuals, including patients with abnormal phenotypes and normal populations. Therefore, determining the clinical significance of a rare or novel copy number change can be challenging. Parental testing may be necessary to further assess the potential pathogenicity of a copy number change.

While most copy number changes observed by chromosomal microarray testing can readily be characterized as pathogenic or benign, there are limited data available to support definitive classification of a subset into either of these categories. In these situations, a number of considerations are taken into account to help interpret results including the size and gene content of the imbalance, whether the change is a deletion or duplication, the inheritance pattern, and the clinical and/or developmental history of a transmitting parent.

All copy number variants within the limit of detection classified as pathogenic or likely pathogenic will be reported regardless of size. This includes but is not limited to incidental findings currently recommended for reporting by the American College of Medical Genetics and Genomics (ACMG).(1) Copy number changes with unknown significance will be reported when at least one protein-coding gene is involved in a deletion greater than 200 kilobases (kb) or a duplication greater than 1 megabase (Mb).

The detection of excessive homozygosity may suggest the need for additional clinical testing to confirm uniparental disomy (UPD) or to test for variants in genes associated with autosomal recessive disorders consistent with the patient's clinical presentation that are present in regions of homozygosity. Interstitial regions with absence of heterozygosity (AOH) of unknown significance will be reported when greater than 10 Mb on UPD-associated chromosomes, and greater than 15 Mb on non-imprinted chromosomes. Terminal AOH will be reported when greater than 5 Mb. Whole genome AOH will be reported when greater than 2% of the genome.

The continual discovery of novel copy number variation and published clinical reports means that the interpretation of any given copy number change may evolve with increased scientific understanding.

Families benefit from hearing genetic information multiple times and in multiple ways. A referral to a clinical genetics professional is appropriate for individuals and families to discuss the results of chromosomal microarray testing.