What is Chromosomal Microarray Analysis?

WHAT IS CHROMOSOMAL MICROARRAY ANALYSIS?

We understand that selecting the right genetic test for your patient can be an overwhelming experience. At Baylor Genetics, we know it’s important to provide you with the most in-depth knowledge, so you are well-equipped to help your patient make an informed decision about their health. Chromosomal microarray analysis (CMA) is a genetic test used to identify chromosomal deletions or duplications in the genome, and in the last twenty years, Baylor Genetics has analyzed over 100,000 microarrays. These missing or additional pieces of chromosome material may explain why your patient has a particular disease. CMA can help healthcare providers determine whether the diseases in patients are caused by microdeletion or microduplication.

“[CMA] may detect a loss or gain of genetic materials that is too small to be detectable by traditional chromosome analysis. These copy number changes may be associated with a disease.” said Dr. Weimin Bi, Division Director of Cytogenetics at Baylor Genetics. “Over the last two decades, we have built up extensive knowledge on which deletions or duplications are associated with human diseases.”

CMA is a high-resolution whole genome test that identifies chromosomal deletions or duplications, otherwise known as copy number variants (CNVs), that are found in the genome and linked to a wide variety of genetic conditions. Baylor Genetics offers several different custom-designed arrays for CMA to meet different demands.

Let’s take a closer look at how CMA is performed at Baylor Genetics.

HOW DOES CHROMOSOMAL MICROARRAY ANALYSIS WORK?

Did you know Baylor Genetics was one of the first laboratories in the nation to perform and offer prenatal CMA? As one of the oldest and most reputable cytogenetics labs in the United States, Baylor Genetics has a team of experts that providers can rely on when ordering CMA for their patients.¹

Providers often order a CMA for patients who present symptoms that include neurodevelopmental abnormalities such as developmental delay, intellectual disability, multiple congenital anomalies, or autism spectrum disorders (ASD).²

To begin testing, a patient must first provide a specimen. We currently accept peripheral blood samples and buccal swabs for postnatal CMA. Once our laboratory receives the sample, your patient’s DNA is extracted and labeled with a color dye. Meanwhile, a control sample is labeled with another color dye and then hybridized with the patient’s sample. Once combined, these labeled samples are placed onto a chip that contains hundreds of thousands of oligonucleotide probes corresponding to many different areas across the genome.

The scanner is used to read the chip and the scanned chip informs any disparity between the patients’ DNA and the reference DNA, more specifically, an abundance of one or the other. A plot visualizes information about the various CNVs (chromosomal deletions or duplications) present in the patient’s genome compared to the reference genome. Our lab team determines whether an identified CNV may explain your patient’s disease, which is based on information in published literature, the CNV databases available to the public, and our own internal databases.

“Everyone has copy number variants in their genome, but we are interested in the ones that are unique that may be causing the disease or phenotype in the individual. We filter the common ones and we are left with unique variants to consider and see if they are causative of the phenotypes in the individual,” said Dr. Nichole Owen, Assistant Clinical Director of Cytogenetics at Baylor Genetics. “A unique variant is not a guarantee it’s related to the phenotype, you can have private familial variants, but unique or rare variants are much more likely to be disease-associated.”

WHAT DO THE RESULTS FOR CHROMOSOMAL MICROARRAY ANALYSIS LOOK LIKE?

Our prenatal CMA testing yields four different results:

1. No clinically significant CNV detected
   • Normal result.
2. Clinically significant CNV detected
   • Known to be associated with a genetic condition.
3. CNV is detected in the fetus but also detected in a parent

Common in about 10 percent of cases and considered low concern – this result should be discussed with a genetic counselor, as this result may signify that the array found a different than expected or unrelated genetic condition

4. Variations of uncertain significance (VUS) were detected in the fetus, but not in either parent.
   • Occurs in about 1-2 percent of cases – requires discussion with a physician or genetic counselor.

Our postnatal CMA testing process yields three different results:

1. No clinically significant CNV detected
   • Normal result.
2. Clinically significant CNV detected
   • Known to be associated with a genetic condition.
3. VUS
   • This result is relatively rare and requires discussion with a physician or genetic counselor.

WHEN SHOULD A CHROMOSOMAL MICROARRAY ANALYSIS BE ORDERED FOR MY PATIENT?

CMA is recommended for individuals thought to have a disease consistent with a chromosomal deletion or duplication. A missing or an extra copy of a piece of a chromosome can arise due to random occurrence or be inherited from a parent. In addition, it may explain why a patient has an ASD, developmental delay, intellectual disability, or multiple congenital anomalies.

In a postnatal setting, a provider may order a CMA test shortly after birth or later during early childhood development. According to Dr. Owen, children with neurodevelopmental disorders may not show signs or symptoms until the child is between the ages of two and five years old, when they begin to exhibit certain observable behaviors, such as those seen with ASD. In addition, CMA is widely acknowledged as a first-tier test in the pediatrics setting.

Expecting parents should consider prenatal CMA “if there are abnormal ultrasound findings or there is an abnormal or atypical non-invasive prenatal testing (NIPT) result,” says Dr. Bi. Prenatal CMA provides further insight into the child’s well-being and can help parents with pregnancy planning, future pregnancies, and prepare them for any additional screenings or special care that may be needed before or after the child is born. The American College of Obstetricians and Gynecologists supports offering CMA through diagnostic testing (amniocentesis or chorionic villus sampling) for any patients “who prefer comprehensive prenatal detection of as many chromosomal aberrations as possible.”³ Additionally, the Society for Maternal Fetal Medicine also put out a consensus statement on CMA as a first-tier test for abnormal ultrasound and products of conception/stillbirth.⁴

BENEFITS OF CHROMOSOMAL MICROARRAY TESTING

Compared to traditional cytogenetic tests, CMA has several advantages.

• CMA can identify significant submicroscopic changes in chromosomes not seen by traditional chromosomal testing.⁵
• CMA provides more precise information on copy number changes due to a high-resolution copy number analysis.
• CMA has a higher diagnostic rate.
• CMA has a shorter turnaround time.
• Typically, CMA does not require dividing cells and can be run on alternative sample types such as buccal swab, tissue and extracted DNA.

LIMITATIONS OF CHROMOSOMAL MICROARRAY ANALYSIS

While there are several benefits to CMA testing, there are a few limitations.

• CMA cannot detect balanced chromosomal rearrangements.
• CMA may not detect small copy number variants below the resolution of the array.
• CMA may not detect copy number changes only seen in a small proportion of cells
• CMA cannot detect single nucleotide changes.

WHAT CHROMOSOMAL MICROARRAY ANALYSIS TESTING OPTIONS DOES BAYLOR GENETICS OFFER?

Baylor Genetics offers prenatal and postnatal CMA.

Prenatal CMA:

• Expanded CMA and/or limited chromosomal analysis
• Targeted CMA and/or limited chromosomal analysis
• Expanded CMA
• Targeted CMA

*Note: The turnaround time (TAT) for Prenatal CMA depends on sample type.

Postnatal CMA:

• Comprehensive CMA – High Resolution (HR) + Single Nucleotide Polymorphism (SNP) (14-day TAT)
• CMA – HR (14-day TAT)

WHERE CAN I LEARN MORE ABOUT CHROMOSOMAL MICROARRAY ANALYSIS?

Having a detailed discussion with your patient about CMA testing can help alleviate any questions or concerns. If you believe your patient may have neurodevelopmental or congenital issues, which could be linked to a chromosomal duplication or deletion, CMA may be their best option. You can find additional information about ordering CMA and how it can help your patient on our website and by reading our blog, “How Ordering the Right Chromosomal Microarray Analysis Can Help Your Patients.”

If you have questions or would like to discuss whether CMA is the right test for your patient, our genetic counselors are happy to speak with you any time so you can provide your patients with accurate information.

We know that our prenatal and postnatal CMA tests can help give your patients the health information they need. Baylor Genetics is committed to research and working with providers to produce the best genetic data available in the industry. We are always learning and working on expanding our testing capabilities, and we want to supply our providers with a wide variety of genetic testing options.

Start an order for CMA.

References:

1. Baylor Genetics. Chromosomal Microarray Analysis. (2022, December 29). https://www.baylorgenetics.com/cma/
2. Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010 May 14;86(5):749-64. doi: 10.1016/j.ajhg.2010.04.006. PMID: 20466091; PMCID: PMC2869000.
3. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020 Oct;136(4):e48-e69. doi: 10.1097/AOG.0000000000004084. PMID: 32804883.
4. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016 Oct;215(4):B2-9. doi: 10.1016/j.ajog.2016.07.016. Epub 2016 Jul 15. Erratum in: Am J Obstet Gynecol. 2017 Feb;216(2):180. PMID: 27427470.
5. American College of Obstetricians and Gynecologists’ Committee on Clinical Guidance—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Microarrays and next-generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology. Committee Opinion No. 682. American College of Obstetricians and Gynecologists. Obstet Gynecol 2016;128:e262–8.