TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: CMAMT    
Chromosomal Microarray, Autopsy/Products of Conception/Stillbirth, Tissue

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

Diagnosis of congenital copy number changes in products of conception, including aneuploidy (ie, trisomy or monosomy) and structural abnormalities

 

Diagnosing chromosomal causes for fetal death

 

Determining recurrence risk of future pregnancy losses

 

Determining the size, precise breakpoints, gene content, and any unappreciated complexity of abnormalities detected previously by other methods such as conventional chromosome and fluorescence in situ hybridization (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

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Hematoxylin and eosin stain review of the paraffin-embedded sample is performed to identify the area of fetal tissue prior to DNA extraction and microarray analysis. If additional FISH testing is requested, it will be performed at an additional charge.

 

A maternal blood sample is requested when ordering this test, see PPAP / Parental Sample Prep for Prenatal Microarray Testing. The PPAP test must be ordered under a different order number than the prenatal specimen

 

Maternal cell contamination (MCC) testing will be performed at no additional charge on the maternal blood and fetal tissue to rule out the presence of maternal cells in the product of conception sample. Testing will not be rejected if maternal blood is not received; however, the possibility of maternal cell contamination cannot be excluded.

 

A paternal blood sample is desired but not required, see PPAP / Parental Sample Prep for Prenatal Microarray Testing.

 

If a fresh specimen is submitted, the test will be cancelled and CMAPC / Chromosomal Microarray, Autopsy, Products of Conception, or Stillborn will be added and performed as the appropriate test.

 

See Frequently Asked Questions: Cytogenetic Testing of Products of Conception by Chromosomal Microarray Analysis in Special Instructions.

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

Chromosomal abnormalities may result in malformed fetuses, spontaneous abortions, or neonatal deaths. Estimates of the frequency of chromosome abnormalities in spontaneously aborted fetuses range from 15% to 60%.

 

Chromosomal microarray (CMA) studies of products of conception (POC), a stillborn infant, or a neonate (autopsy) may provide useful information concerning the cause of miscarriage or fetal loss. In addition, CMA may provide information regarding the recurrence risk for future pregnancy loss and risk of having subsequent children with chromosome anomalies. This is particularly useful information if there is a family history of 2 or more miscarriages or when fetal malformations are evident.

 

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 over 220,000 markers for the detection of copy number changes and regions with absence of heterozygosity. Identification of regions of excess homozygosity on a single chromosome could suggest uniparental disomy that may warrant further clinical investigation when observed on chromosomes with known imprinting disorders. In addition, the detection of excess homozygosity on multiple chromosomes may suggest consanguinity.

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.

Interpretation Provides information to assist in interpretation of the test results

Copy number variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

While many 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, making interpretation of these variants challenging. In these situations, a number of considerations are taken into account to help interpret results including the size and gene content of the imbalance, as well as whether the change is a deletion or duplication. Parental testing may also be necessary to further assess the potential pathogenicity of a copy number change. In such situations, the inheritance pattern and clinical and developmental history of the transmitting parent will be taken into consideration.

 

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 1 megabase (Mb) or a duplication greater than 2 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. Regions with absence of heterozygosity (AOH) of unknown significance will be reported when greater than 5 Mb (terminal) and 10 Mb (interstitial) on UPD-associated chromosomes. Whole genome AOH will be reported when greater than 10% 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.

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

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 low-level 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 varaints such as epigenetic changes.

 

The results of this test may reveal incidental findings unrelated to the original reason for referral. In such cases, studies of additional family members may be required to help interpret the results.

Supportive Data

The array was validated by testing 25 formalin-fixed, paraffin-embedded products of conception specimens previously tested using FISH analysis. All abnormalities previously identified by another methodology were confirmed.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Kalia, S., Adelman, K., Bale, S. et al: Recommendations for reporting of secondary findings in clinical exome and genome sequencing. 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med 2017;19:249-255

2. American College of Obstetricians and Gynecologists Committee on Genetics: Committee opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013;122:1374-1377

3. Wapner RJ, Martin CL, Levy B, et al: Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367:2175-2184

4. Armengol L, Nevado J, Serra-Juhe C, et al: Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis. Hum Genet. 2012;131:513-523

5. Laurino MY, Bennett RL, Saraiya DS, et al: Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2005;14:165-181

6. Reddy UM, Page GP, Saade GR, et al: Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med. 2012;367:2185-2193

Special Instructions Library of PDFs including pertinent information and forms related to the test