Chromosomal microarray can provide important information for patient treatment

Chromosomal microarray (CMA)—a powerful test for diagnosing the genetic abnormalities causing some types of developmental delay and birth defects—can be used in an evidence-based manner to provide important information for patient treatment, according to a pair of studies in the September issue of Genetics in Medicine, the official peer-reviewed journal of The American College of Medical Genetics. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

The new papers address criticisms that CMA testing, though highly accurate, doesn't alter the clinical management of affected children. "Together, the two new studies show that CMA tests are clinically important and helpful, and provide important information about how to interpret these advanced genetic tests in an evidence-based manner," comments Jim Evans, M.D., Ph.D., Editor-in-Chief of Genetics in Medicine.

CMA Tests Provide Useful Information for Patient Care

Chromosomal microarray testing works by detecting small DNA variations—either deletions or repetitions—called copy-number variants (CNVs). In recent years, CMA tests have revolutionized the ability of medical geneticists to detect clinically significant CNVs in children with intellectual disability or developmental delay (ID/DD), autism spectrum disorders, or multiple congenital anomalies.

However, some experts have questioned whether the precise genetic information provided by CMA actually leads to any changes in treatment. In some cases, health insurers have restricted the use of or reimbursement for CMA in children with ID/DD or other conditions. "The rationale behind these decisions is that CMA should not be reimbursed because it is only used to clarify a diagnosis but does not change clinical management of the patient," write Dr. Mira Irons and colleagues of Children's Hospital Boston.

To address this question, Dr. Irons and coauthors evaluated the results of CMA tests performed in 1,729 children with ID/DD or other disorders over a one-year period. The CMA results were "clinically relevant" in approximately 13 percent of patients. Testing showed a known genetic abnormality in about seven percent of children and a "possibly significant" variant in six percent.

The results provided important information for medical management in 54 percent of children with known abnormal variants and 34 percent of those with possibly significant variants. "CMA results influenced medical care by precipitating medical referrals, diagnostic imaging, or specific laboratory testing," the researchers write.

In the second study, Christa L. Martin, Ph.D., of Emory University and colleagues assessed the clinical and functional significance of CNVs in children with ID/DD, based on a database of nearly 16,000 patients. Because most genetic abnormalities leading to ID/DD are rare, very large numbers of patients are needed to draw meaningful conclusions. The data was contributed by the International Standards for Cytogenomic Arrays (ISCA) consortium, which includes more than 150 clinical laboratories worldwide.

The results showed CNVs occurring repeatedly in 20 different regions—strongly suggesting that abnormalities in these regions were causing clinical cases of ID/DD. The researchers conclude that, of 28 recurrent CNVs identified in the study, 21 are definitely associated with clinical ID/DD in need of evaluation and diagnostic testing.

Overall, CMA detected CNV abnormalities in 17.1 percent of this very large group of children with ID/DD. The ISCA consortium plans to continue collecting data on CMA test results, and to make the full database publicly available to researchers and the clinical community. Dr. Martin and coauthors conclude, "This data will provide an evidence-based guide to clinicians across many disciplines involved in the diagnosis, management, and care of these patients and their families."

Source: Genetics in Medicine