A chromosomal microarray (CMA) is a genetic test that examines a person’s DNA for specific types of changes. This test helps identify if medical conditions are caused by missing or extra pieces of chromosome material. It is also known by other names, such as array comparative genomic hybridization or SNP microarray.
Types of Genetic Changes Detected
CMA primarily detects copy number variants (CNVs), which are segments of DNA that are either duplicated (extra copies) or deleted (missing copies). These CNVs are often submicroscopic, meaning they are too tiny to be observed with traditional methods. Despite their size, these changes can significantly affect health, learning, or development.
The test can identify changes as small as 5-10 kilobases (Kb), offering a resolution up to 1000 times higher than conventional karyotyping. CMA compares a patient’s DNA sample to a normal control sample to find these minute differences.
Beyond CNVs, CMA can also detect whole chromosome aneuploidies, such as Trisomy 21 (Down syndrome), where there is an abnormal number of entire chromosomes. It can also identify regions of homozygosity (ROH), which are stretches of DNA where both copies of a chromosome segment are identical. ROH can sometimes indicate parental relatedness or an increased risk for certain recessive genetic conditions.
When Chromosomal Microarray is Recommended
A healthcare provider may suggest a CMA test to investigate the underlying cause of certain health or developmental concerns. It is often recommended for children with unexplained developmental delay, intellectual disability, or autism spectrum disorder, serving as a diagnostic tool for these neurodevelopmental conditions.
CMA is also recommended for individuals with significant dysmorphic features or multiple congenital anomalies that do not fit a specific, well-defined genetic syndrome. It is applied in prenatal diagnosis, especially when ultrasound examinations reveal anomalies in a developing fetus. CMA can also be utilized in cases of stillbirth or neonatal death to determine a genetic cause.
How Chromosomal Microarray Differs from Other Genetic Tests
CMA offers a different level of detail compared to other genetic tests. Traditional karyotyping, which involves looking at chromosomes under a microscope, can detect large changes in chromosome structure or number, such as translocations or large deletions and duplications. However, CMA provides much higher resolution, enabling the detection of submicroscopic deletions and duplications that karyotyping would likely miss.
Fluorescence In Situ Hybridization (FISH) is another genetic test, but it is targeted, meaning it looks for specific genetic changes in particular regions of chromosomes. In contrast, CMA scans the entire genome, providing a broader overview of copy number changes across all chromosomes. CMA does not detect balanced chromosome rearrangements, such as balanced inversions or translocations, where there is no net gain or loss of DNA.
Exome or genome sequencing are more detailed tests that focus on detecting very small changes in DNA, such as single nucleotide variants or small insertions and deletions. While sequencing looks at the specific sequence of DNA bases, CMA is designed to identify larger-scale copy number variations. If CMA does not identify a cause for an intellectual disability, whole exome sequencing may then be considered.
Understanding Chromosomal Microarray Results
The results of a chromosomal microarray test are categorized to help patients and families understand their implications. A “pathogenic” result indicates that a genetic change is known to cause a specific disease or condition. A “likely pathogenic” result suggests that the genetic change is very likely to be disease-causing, based on available evidence.
A “variant of uncertain significance” (VUS) means the clinical meaning of the detected genetic change is currently unclear. These VUS results can pose challenges for families as they do not provide a definitive answer regarding a diagnosis. “Likely benign” results suggest the genetic change is probably not disease-causing, while “benign” indicates it is not associated with a disease.
Many copy number variants found by CMA are harmless and may not be reported. When a genetic change is found, further testing of parents and other family members may be recommended to determine if the change was inherited or if it arose spontaneously. Genetic counseling is an important step in interpreting CMA results, providing families with a comprehensive understanding of the findings and their future implications.