Top Things to Know: Genetic Testing for Heritable Cardiovascular Diseases in Pediatric Patients
Published: August 20, 2021
Prepared by Katherine A. Sheehan, PhD, Science and Medicine Advisor
- Decisions surrounding the scope and timing of pediatric genetic testing have broad and complex implications for the child and other family members in the diagnosis and management of heritable cardiovascular diseases including cardiac channelopathies, cardiomyopathies, aortopathies, dyslipidemias and structural diseases. Yet most clinical guidance is aimed at adult patients.
- This scientific statement draws upon existing clinical practice guidelines, scientific statements, and key studies in the field to provide guidance for clinicians on issues of pediatric genetic testing including timing, consent, family dynamics, and other issues.
- The basics of clinical cardiovascular genetic testing incudes methods to analyze changes in genes or chromosomes at the DNA level within two common categories: cytogenetic testing, which involves analysis at the chromosome level to evaluate suspected congenital heart defects associated with other clinical concerns, and molecular genetic testing including next-generation sequencing technologies for detection of diseases controlled by a single gene, such as cardiomyopathies and channelopathies.
- Genetic testing is generally performed either for diagnostic reasons, where a positive genetic test confirms an existing clinical suspicion for disease in a patient, or risk-predictive purposes, where the identification of a pathogenic or likely pathogenic gene variant in a symptomatic patient has also been identified in an asymptomatic family member, suggesting the latter is at risk for developing the disease.
- Risk predictive genetic testing is the basis for family cascade testing programs, which involves testing additional at-risk relatives of a family member affected by disease. Those who have the genetic risk are referred for risk-reducing medical management and family counseling.
- Genetic testing in children is more involved than in adults. Reasons include their vulnerability as a population, and the uncertainty surrounding development of disease in those who have positive risk testing, as nearly all genetic cardiovascular diseases have incomplete penetrance and vary in manifestation. Thus, for children the balance of benefits and harms of genetic testing must be carefully considered and potentially delayed until the child is old enough to provide assent unless there is an appropriate childhood intervention available.
- Referral of pediatric patients to specialized, multidisciplinary clinical cardiovascular genetics programs has the advantage of providing integrated evaluation and management including taking of personal and family histories, physical examination, cardiac testing interpretation, genetic counseling, psychological assessment and cascade testing for at-risk relatives to ensure optimal care for families with heritable cardiovascular disorders.
- Detailed information for specific heritable disorders is provided to help guide clinicians in genetic testing, interpretation of results and care for pediatric patients and their families. These include cardiac channelopathies, cardiomyopathies, heritable aortopathies, familial dyslipidemias, congenital heart disease, and several cases special to pediatrics.
- Pediatric genetic testing has important considerations beyond those of adult testing, including the vulnerability of children as a population, dynamics within the child’s family, the current state of genetic testing methods, the characteristics of each type of heritable cardiovascular disease, its likelihood and timing of manifestation, and the availability, cost, and potential psychosocial effects of interventional treatments. These are all factors that help inform the decision-making process to ensure the best outcomes for children and family members.
- Clinicians caring for pediatric patients at risk of heritable cardiovascular disease will benefit from the collated insights and guidance in this scientific statement, covering all aspects of care from assessment, shared decision making and assent for genetic testing of the child and family, to genetic counseling, timing and likelihood of disease onset, treatment options and psychosocial impact on all family members.
Citation
Landstrom AP, Kim JJ, Gelb BD, Helm BM, Kannankeril PJ, Semsarian C, Sturm AC, Tristani-Firouzi M, Ware SM; on behalf of the American Heart Association Council on Genomic and Precision Medicine; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Lifestyle and Cardiometabolic Health. Genetic testing for heritable cardiovascular diseases in pediatric patients: a scientific statement from the American Heart Association. Circ Genom Precis Med. 2021;14: e000086. doi: 10.1161/HCG.0000000000000086