A better genetic test for developmental disabilities

David Miller, MD, PhD
David Miller, MD, PhD

Traditional genetic testing identifies chromosomal duplications or deletions in about 3 percent of children suffering from unexplained developmental disabilities. Now, using a cutting-edge tool called a chromosomal microarray, physicians can increase that number to about 15 percent – giving answers to potentially tens of thousands more children.

More than 3 percent of children are born with developmental disabilities that have no obvious cause. These children often baffle physicians because medical history and a physical exam are just not always enough to diagnose them. “When we see a patient, we go down our checklist of the usual suspects,” says David Miller, MD, PhD, clinical geneticist in the Division of Genetics at Children’s Hospital Boston. “If we get to a point where we still can’t put our finger on anything, that’s when we turn to this type of testing.”

There are hundreds of chromosome deletions or duplications that result in birth defects or developmental disabilities such as autism. By zeroing in on the exact cause, physicians may be able to determine which specialists need to be added to the team and how best to treat them.

“If you know they have this large chromosomal change, you can help the parents know what to expect,” says Miller, “what is the achievable outcome of their child.”

The traditional test, called a karyotype, allows genetics experts to take a good hard look at the chromosomes and identify regions that are missing or are duplicated. A chromosomal microarray analysis can do the same thing but at much higher resolution, enabling genetic imbalances to be identified in more children at comparable cost.

A positive test result for an autistic child.   A chromosomal microarray analysis indicates this child has a duplication (red) on chromosome 15. This region of chromosome 15 is frequently duplicated in autistic children.
A positive test result for an autistic child. A chromosomal microarray analysis indicates this child has a duplication (red) on chromosome 15. This region of chromosome 15 is frequently duplicated in autistic children. Courtesy of Yiping Shen, PhD, and Bai-Lin Wu, PhD.
Here at Children’s, physicians routinely order a chromosomal microarray analysis. However, in far too many places in the country, physicians are limited to the older, less sensitive test; in some cases because the more effective one is not an option.

“We are already ordering this testing as a clinical standard of care, but if you look around,” says Miller, “there are parts of the country where people are being told by insurance companies: You can’t order a chromosomal microarray, its experimental.”

In a consensus statement published yesterday in the American Journal of Human Genetics, Dr. Miller and colleagues of the International Standard Cytogenomic Array Consortium urge heath care providers to make the chromosomal microarray test standard practice for diagnosing children suffering from developmental disabilities. Dr. Miller, who published a study last month demonstrating that this test is at least three times more effective than a karyotype in identifying genetic causes of autism, hopes that this consensus statement will encourage more doctors to make the chromosomal microarray their test of choice, and that more insurance companies will cover the costs.

“For the last 35 years, people have considered the karyotype the standard of care,” says Miller. “We are trying to say – it’s time to change our thought process.”