Genes may show which child heart patients need extra help

Half of children with severe heart defects also experience learning disabilities or other neurodevelopmental delays. These have been blamed partly on the stress of heart surgery the kids undergo early in life and on impaired blood flow during pregnancy.

A new study finds evidence for an additional culprit, one that had long been suspected: genetics.

The study, whose authors included researchers at Children's Hospital of Philadelphia, identified a series of mutations that were significantly more prevalent in children with both heart and brain problems than in those with heart problems alone.

The findings, to be published in Friday's issue of the journal Science, offer hope for earlier identification of children who are at risk of falling behind in school. That would allow earlier intervention in the form of tutors, therapy, and other services, said the authors, from Harvard, Yale, and Columbia Universities and other institutions.

Currently, early diagnosis of neurodevelopmental problems can be tricky, because they can be subtle and the brains of such children may appear normal on an MRI, said CHOP cardiologist Elizabeth Goldmuntz, one of the study's main contributors.

More research is needed to replicate the findings before they could be used in an early screening test, but the concept is promising, she said.

"We could try to identify the higher-risk population and therefore intervene earlier on, when the brain is still developing and we have opportunities to have maybe a lasting impact," Goldmuntz said.

Schools sometimes do not identify learning delays or figure out an appropriate strategy until children reach second or third grade, said Daniel Bernstein, a cardiologist at Lucile Packard Children's Hospital Stanford.

"Imagine if you could intervene in pre-K," said Bernstein, who was not involved in the study.

In a sample of more than 1,200 patients, the authors identified damaging mutations in several dozen genes that were associated with both heart defects and other issues - either neurodevelopmental delays or anomalies in some other organ.

All were "de novo" mutations, meaning they appeared in the children and not in either parent.

The mutations were twice as common in children with both heart defects and neurodevelopmental delays when compared with a control group. The mutations were three times as common in children with both heart defects and one of the anomalies in other organs.

And the mutations were five times as common in children with heart defects who had both a neurodevelopmental delay and an anomaly in another organ.

That suggests the genes play a fundamental role, said Harvard's Christine Seidman, one of the paper's main authors.

"These genes are not specific to a particular organ's biological development," said Seidman, director of the Brigham & Women's Cardiovascular Genetics Center in Boston. "Rather, these are master regulators."

Jodi Lemacks, whose son Joshua traveled from Richmond, Va., to CHOP for multiple heart operations, said she was encouraged by the study.

The operations went well for Joshua, who was born with hypoplastic left heart syndrome, but he experienced delays when learning to read in first grade. Armed with information from the American Heart Association, his mother persuaded school officials to get him extra help.

Now 12, Joshua is on his school's honor roll, said his mother, who is national program director of Mended Little Hearts, a support group. Even earlier intervention could only help other children, she said.

"These kids have enough challenges as it is," Lemacks said. "If you can help them be as successful as possible, then it really does improve their quality of life."

Heart defects are the most common birth defect, affecting nearly 1 percent of children - about 40,000 births in the United States each year, though many are fairly minor. The patients in the study had moderate to severe heart defects, generally meaning they needed surgery or some intervention in the first year of life.

tavril@phillynews.com

215-854-2430@TomAvril1