Gene mutations found in many children with abnormally thick heart muscles

Most children with unexplained thickening of the heart muscle, called idiopathic cardiac hypertrophy, actually have a genetic mutation that affects cells that help the heart to contract, said researchers from Baylor College of Medicine and Harvard Medical School in a report that appears online in the New England Journal of Medicine today.

Gene mutations were found in nearly half of the children whose heart problem seemed sporadic (and are not found in other family members) and in two-thirds of those children with the thickened heart muscle whose families have a history of similar problems, said Dr. Jeffrey A. Towbin, professor of pediatrics-cardiology at BCM and chief of pediatric cardiology and director of cardiomyopathy and heart failure treatment services at Texas Children’s Hospital and an author of the report along with researchers from Harvard Medical School. This was unexpected in young children, a group previously thought to have heart thickening that differs substantially from that seen in adults.

The findings may spur doctors to pursue genetic analysis and family evaluations in children with this problem, said Towbin, who is also director of the Phoebe Willingham Muzzy Pediatric Molecular Cardiology Laboratory at Texas Children’s Hospital. This thickening of the heart muscle can be the cause of sudden death in children and young adults while playing sports or doing ordinary activities, he said.

"This is the disease that would be the most likely cause of sudden unexplained death in young, healthy, and commonly active or athletic individuals," said Towbin. "When someone dies of this problem and it is the first sign that it exists in a family, it would behoove us to find out the risk in the rest of the family. That’s a step in the direction of personalised medicine. We want to have an approach toward an evaluation that, in the proper situation, now includes genetic testing."

In this study, researchers from Baylor College of Medicine and Texas Children’s Hospital and Harvard Medical School, including senior authors Drs. Jonathan G. Seidman and Christine E. Seidman analysed the family and medical histories of 63 boys and 21 girls who had cardiac hypertrophy or thickening of the heart muscle that was diagnosed before the youngsters reached age 15, many in the first years of life.

The researchers analysed the genetic sequences of eight genes associated with proteins involved in the sarcomere, the layer of cells crucial to the heart’s ability to contract and pump blood. When these genes are mutated, they are known to cause heart muscle disease in adults called hypertrophic cardiomyopathy.

The scientists also sequenced two genes associated with metabolic proteins. When these genes are mutated they can also cause overgrowth of the heart’s ventricle, the major pumping chamber.

The scientists found gene mutations in 25 of 51 children who had cardiac hypertrophy but no family history of heart problems and in 21 of 33 such children who had a family history of heart muscle weakness.

Children who had genetic mutations were more likely to undergo heart transplant or to suffer sudden death than those who had no identified genetic mutations. Children who had a family history of heart muscle problems were more likely to have implanted defibrillators that automatically shock a heart that goes into a dangerous rhythm.

Others who took part in this study include Andres Menesses-Diaz of Baylor College of Medicine and Texas Children’s Hospital, Hiroyuki Morita, Heidi L. Rehm, Barbara McDonough, Amy E. Roberts and Raju Kucherlapati, of Harvard Medical School.

Funding for this study came from the Howard Hughes Medical Institute, the National Heart, Lung and Blood Institute, the NFL Charities Foundation, TexGen and the Children’s Cardiomyopathy Foundation.

(Source: New England Journal of Medicine: Baylor College of Medicine: April 2008)