Many children with cardiomyopathy have a genetic mutation but few are screened – UB Now: News and views for UB faculty and staff

A national UB-led study of genes in pediatric cardiomyopathy shows strong evidence for routine genetic screening in children with the disease. The study, published April 28 in the Journal of the American Heart Association, revealed wide variation in screening, with some centers performing routine genetic testing and others doing none.

The National Institutes of Health-funded study of 152 children with cardiomyopathy, conducted at 14 centers, found that only half had undergone genetic screening. Of those who did not undergo screening, 21% were found to have a genetic cause for the disease after undergoing genetic testing as part of the research study.

“Even in families without a family history of cardiomyopathy, we found that many children with cardiomyopathy have a genetic cause that we can identify,” said Steven E. Lipshultz, the study’s senior author and principal investigator, and A. Conger Goodyear Professor and Chair from the department of pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University Library.

The lead author on the paper is Stephanie M. Ware of Indiana University School of Medicine.

The findings of the study are critical to the treatment and potentially cure of this rare, sometimes fatal, pediatric disease. “We had assumed that many of the life-threatening cardiomyopathies in children were due to genetic mutations,” explains Lipshultz. “This research confirms that assumption. Knowing the cause can help us treat these children more effectively and, in some cases, even cure them with therapies targeting the specific mutation that causes their disease. “

Genetic screening can provide families with vital, life-saving information, Lipshultz says.

“Since some mutations are associated with rapidly progressing fatal outcomes, genetic screening could allow children with these mutations to be identified and prioritized for a life-saving heart transplant,” he says.

Information about which mutation may be involved in a patient’s disease can also make a significant difference in the type of treatment being prescribed – and the outcome. Lipshultz notes that he and his colleagues have published research showing that children whose cardiomyopathy results from certain mutations that cause heart failure will worsen and even die if treated with therapies commonly prescribed for heart failure.

“This is because those therapies push the child’s genetically compromised mitochondria to work harder,” says Lipshultz. “This can tragically hasten the demise of these children. But knowing that these types of mutations are present allows alternative therapies to be used that preserve and protect mitochondrial function. This is one of many examples where knowing the genetic cause of cardiomyopathy can make the difference between the life or death of a child. “

The study also identified new gene mutations related to cardiomyopathy.

Although the study was conducted in large pediatric hospitals with established cardiomyopathy programs, only a few of them used genetic screening as a routine part of clinical care. Nationally, a minority of children and their families with cardiomyopathy have the option of undergoing genetic screening, a fact that Lipshultz and his co-authors hope this study will begin to change.

For example, UB is one of only 40 cardiomyopathy centers in the world that have been critically and rigorously reviewed and certified as a recognized cardiomyopathy care center by the Children’s Cardiomyopathy Foundation to provide quality cardiac care and specialized disease management to children with cardiomyopathy. (This study also received funding from the Children’s Cardiomyopathy Foundation.) At UB and John R. Oishei Children’s Hospital, funding from federal and private sources provides additional funding for more research and clinical care in pediatric cardiac clinical genetics, as well as genetic engineering. accompaniment.

Lipshultz adds that unfortunately, most children with the disease are not cared for in these specialized centers.

“One hurdle is that cardiologists and geneticists are interested in ordering these genetic tests and then advising families on the results,” he says. “Testing the most common gene mutations associated with cardiomyopathy can be done virtually anywhere as lab companies provide the kits for collected patient samples.”

The study supports existing clinical guidelines for pediatric cardiomyopathy, but, Lipshultz points out, these are not widely followed. “Our results show that, by routine clinical judgment, a high percentage of children with genetic causes for their cardiomyopathy are missing,” he says, adding, “If you’re not looking, you don’t know.”

The results also provide additional evidence for cardiac surveillance, where all immediate family members of a child with cardiomyopathy and an associated gene mutation are screened to find out if they too have the same mutation and cardiomyopathy.

At a time when gene-targeted therapies that can optimize care and planning are increasingly possible, it is no longer justifiable to screen these patients genetically, Lipshultz says.

In the study, the researchers performed complete exome sequencing in a large number of children with cardiomyopathy. Full exome sequencing is a much more comprehensive way to identify gene mutations than simply looking for the six or eight most common mutations known to be related to cardiomyopathy, Lipshultz explains.

“Whole exome sequencing can identify a much broader range of pathological mutations and identify new new mutations that may be related to cardiomyopathy,” he says.

Lipshultz is an international leader whose research has led to significant evidence-based improvements in the treatment of patients with pediatric cardiomyopathy and related diseases. In addition to his role at Jacobs School, Lipshultz serves as pediatric chief of service at Kaleida Health, medical director of pediatric services business development at John R. Oishei Children’s Hospital, and president of UBMD Pediatrics.

In addition to Ware and Lipshultz, other co-authors of the Pediatric Cardiomyopathy Registry Study Group are from UB; Vanderbilt University; University of Tabuk; Harvard University; New England Research Institutes; Washington University, St. Louis; Einstein College of Medicine; University of Colorado; University of Southern California; Columbia University; University of Tennessee; University of Pennsylvania; Northwestern University; University of Miami; University of Utah; University of Cincinnati; and Wayne State University.

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