Link between Congenital Heart Disease and Neurodevelopment Issues in Children Found
December 3, 2015 - 4:23 PM
Scientists have confirmed the role of a set of gene mutations in the
development of congenital heart disease and simultaneously discovered a
link between them and some neurodevelopmental abnormalities in children.
These abnormalities include cognitive, motor, social, and language
“The risk of developing neurodevelopmental disabilities is so high
when these particular gene mutations are present that we might consider
testing for them in all patients with congenital heart disease,” said
Jonathan R. Kaltman, M.D., a study investigator and program
administrator of the National Heart, Lung, and Blood Institute’s (NHLBI)
Bench to Bassinet Program, which funded the study. Dr. Kaltman noted
that the findings from the study would have to be replicated and refined
before a clinical test could be available. NHLBI is part of the
National Institutes of Health.
Congenital heart disease — in which there are structural defects in
the heart — is the most common type of birth defect in the United
States, and one of the leading causes of infant death. Nearly 40,000
children are born with congenital heart disease each year, and experts
estimate that approximately 1 to 2 million adults and 800,000 children
in the U.S. currently live with the disease.
“Surgery is often performed early in life to repair heart defects,”
said Dr. Kaltman. “However, we have found that once children reach
school age, many exhibit various attention deficits, including attention
deficit hyperactivity disorder, and other neurobehavioral problems.”
In their study, published Dec. 4 in the journal Science (link is external),
investigators from the Bench to Bassinet Program’s Pediatric Cardiac
Genomics Consortium used a technique called exome sequencing to
genetically evaluate 1,220 family trios — composed of a child with
congenital heart disease and the mother and father. Through this
technique, which examines only the protein-coding regions of DNA, they
found that children with moderate-to-severe congenital heart disease had
a substantial number of “de novo” gene mutations. De novo mutations
occur within egg, sperm, and fertilized cells, but are not part of the
genetic makeup of the mother or father.
“This finding was especially high in patients who had congenital
heart disease and another structural birth defect and/or a
neurodevelopmental abnormality,” said senior investigator Christine
Seidman, M.D., of Brigham and Women’s Hospital, Howard Hughes Medical
Institute, and Harvard Medical School, Boston. “When the consortium
examined the specific genes involved, many of them were highly expressed
in both the developing heart and brain, suggesting that a single
mutation can contribute to both congenital heart disease and
Dr. Seidman noted that the findings have implications for basic
research and clinical medicine. “Through further analyses of these
mutated genes, we expect to uncover new pathways that are critical for
the development of the heart, brain, and other organs — information that
will contribute basic insights into the causes of many human congenital
malformations,” she said.
Dr. Seidman added that if the relationship between the de novo
mutations and neurodevelopmental abnormalities in children continues to
hold, clinical genetic tests could be created for newborns with
moderate-to- severe congenital heart abnormalities. The patients found
to carry the gene mutations could then be targeted for greater
surveillance and early interventions that might address and limit
developmental delays and improve their outcomes.
The National Heart, Lung, and Blood Institute (NHLBI)
plans, conducts, and supports research related to the causes,
prevention, diagnosis, and treatment of heart, blood vessel, lung, and
blood diseases; and sleep disorders. The Institute also administers
national health education campaigns on women and heart disease, healthy
weight for children, and other topics. NHLBI press releases and other
materials are available online at www.nhlbi.nih.gov.
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