Friday, May 18, 2018

First-Line Genetic Test for Autism: CMA

General

Chromosomal Microarray Analysis (CMA): A first-line diagnostic test in autism

What is a Chromosomal Microarray Analysis (CMA)?

Chromosomal microarray analysis is a high-resolution genetic test that can identify small regions of abnormalities in chromosomes.

Chromosome are made up of DNA. DNA is the biological material that encodes our genetic information. A gene is a region of DNA within a chromosome that encodes a protein which then performs specific functions in the body. Most of the cells in our bodies have 46 chromosomes (23 pairs). One of each pair is from the mother, and the other is from the father. The first 22 pairs are the same in males and females. The last pair (called the sex chromosomes) differ in males and females: females have two X chromosomes and males have one X and one Y chromosome.

There are many different ways of analyzing an individual’s genetic information. CMA is designed to detect small regions of abnormalities called copy number variants (CNV). A copy number variant (CNV) is a change to the expected amount of DNA in a chromosome. In general each person should have two copies of each chromosome in their cells; one is inherited from each parent. A CNV is when a region of the chromosome is found to have either less than or more than two copies. On occasion, an individual may have an extra copy (duplication) or a missing copy (deletion) of an entire chromosome. More often, the extra piece or missing piece involves a small region or a chromosome, and not the entire chromosome. When this is the case, it is referred to as a copy number variant (CNV).

Who should have this test?

Chromosomal microarray analysis is recommended for individuals with a diagnosis of Autism Spectrum Disorder, Intellectual Developmental Disorder, or Global Developmental Delay. The American Academy of Pediatrics and the American College of Medical Genetics have included this test in their recommended evaluation of a child presenting with one or more of these diagnoses. This test may also be recommended for individual with multiple congenital anomalies or epilepsy.

In the past, individuals with these conditions would have received a test called a karyotype which looks at the chromosomes at low resolution. The yield of this test was low (around 3-5%). The chromosomal microarray analysis is now recommended instead of the karyotype as it provides a much higher resolution of analysis and has a much higher yield (around 10-20%). In about one-third of those with a genetic finding on CMA, the findings are “actionable,” meaning that they lead to changes in medical management. If a duplication or deletion is detected, the next step is to look at what genes are present in the region of the duplication or deletion. By identifying those genes, we can better understand an individual’s unique biology.

What is required for the test?

A sample of DNA is needed from the patient and can be obtained by a cheek swab, saliva, or blood.

Are there other names for this test?

The technique used in this test is referred to as comparative genomic hybridization (CGH); therefore, this test is sometimes referred to as array comparative genomic hybridization (aCGH). This test is also referred to in some laboratories as an Oligo-SNP Chromosomal Array.

Once the test is done, how soon are results available?

Results are usually available within 6 weeks

Is this test covered by insurance?

Because CMA is now widely recommended for all individuals with a diagnosis of autism, intellectual developmental disorder, or global developmental delay, most insurance plans provide coverage for this test. Please contact your insurance plan’s customer service line to find out your specific benefits. Most laboratories that run this test provide excellent customer service and can help you understand your plan’s benefits. Some laboratories, including Lineagen, will not run the test until they have informed you of your insurance benefits and you have approved any out-of-pocket expense.

What other genetic tests are available?

Many other genetic tests are also available, but CMA is the only first-line genetic test recommended for all individuals with autism, intellectual developmental disorder, or global developmental delay.

Other genetic tests that you’re practitioner may recommend are Whole Exome Sequencing, sequencing of specific individual genes or panels of genes, or SNP testing (such as 23 and me).

Where can I find more information?

Your physician or nurse practitioner can help to answer any questions you have. Genetic counselors are also available through the laboratories that perform these tests. Additional information can be found in these publications:

Ellison, JW, et al. Clinical Utility of Chromosomal Microarray Analysis. Pediatrics. Volume 130, Number 5. November, 2012. Pages e1085-e1095.

Johnson, CP, et al. Identification and Evaluation of Children with Autism Spectrum Disorder. Pediatrics.Volume 120, Number 5. November, 2007. (Practice Guideline of the American Academy of Pediatrics)

Schaefer, GB and Mendelsohn, NJ. Clinical Genetics Evaluation in Identifying the Etiology of Autism Spectrum Disorders. Genetics in Medicine. March, 2013. (Practice Guideline of the American College of Medical Genetics)