Interpretive Handbook

Test 61835 :
Chromosomal Microarray, Congenital, Blood

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 >1.9 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.


As a participant in the International Standard Cytogenomic Array Consortium (ISCA) (see Chromosomal Microarray Testing and the ISCA Consortium Database in Special Instructions), Mayo Clinic Cytogenetics Laboratory contributes submitted clinical information and test results for molecular cytogenetic tests to a HIPAA-compliant, deidentified public database hosted by the National Institutes of Health. This is an international effort to improve diagnostic testing and our understanding of the relationships between genetic changes and clinical symptoms (for information about the database visit the consortium website at Confidentiality of each specimen is maintained. Patients may request to opt-out of this scientific effort by calling the laboratory at 800-533-1710, extension 8-2952, and asking to speak with a laboratory genetic counselor. Please call with any questions.


An online research opportunity called GenomeConnect ( is available for the recipients of genetic test results. This patient registry collects deidentified genetic and health information to advance knowledge of genetic variants. See GenomeConnect Patient Portal in Special Instructions for more information.

Useful For Suggests clinical disorders or settings where the test may be helpful

First-tier, postnatal test for individuals with multiple anomalies that are not specific to well-delineated genetic syndromes, apparently nonsyndromic developmental delay or intellectual disability, or autism spectrum disorders as recommended by the American College of Medical Genetics


An appropriate follow-up test for individuals with unexplained developmental delay or intellectual disability, autism spectrum disorders, or congenital anomalies with a previously normal conventional chromosome study


Determining the size, precise breakpoints, gene content, and any unappreciated complexity of abnormalities detected by other methods such as conventional chromosome and FISH studies


Determining if apparently balanced abnormalities identified by previous conventional chromosome studies have cryptic imbalances, since a proportion of such rearrangements that appear balanced at the resolution of a chromosome study are actually unbalanced when analyzed by higher-resolution chromosomal microarray


Assessing regions of homozygosity related to uniparental disomy or identity by descent

Interpretation Provides information to assist in interpretation of the test results

When interpreting results, the following factors need to be considered:

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 or developmental history of a transmitting parent.


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.


The detection of excessive homozygosity may suggest the need for additional clinical testing to confirm uniparental disomy or to test for mutations in genes associated with autosomal recessive disorders consistent with the patient's clinical presentation that are present in regions of homozygosity.


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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 mutations, small deletions or insertions below the resolution of this assay, or other types of mutations such as epigenetic changes.


The results of this test may be of uncertain clinical significance. In such cases, studies of additional family members may be required to help interpret the results.


Interfering factors:

-Use of an improper anticoagulant (sodium heparin 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

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Manning M, Hudgins L: Professional Practice and Guidelines Committee: Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010;12(11):742-745

2. Miller DT, Adam MP, Aradhya S, et al: Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86:749-764

3. Kearney HM, Thorland EC, Brown KK, et al: Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med 2011;13(7):680-685

4. Kearney HM, Kearney JB, Conlin LK: Diagnostic implications of excessive homozygosity detected by SNP-based microarrays: consanguinity, uniparental disomy, and recessive single-gene mutations. Clin Lab Med 2011;31(4):595-613