Three year experience of a clinical cardiovascular genetics program for infants with congenital heart disease

Abstract

Objective To describe the first 3 years of experience of having an inpatient “cardiogenetics” program which involves medical geneticist assessment of infants with major congenital heart disease (CHD) requiring surgical intervention in the first year of life. Patients Patients less than a year of age admitted to Children's Hospital of Wisconsin's Herma Heart Institute for surgical intervention for CHD seen by the cardiogenetics program. Patients with major trisomies (13, 18, and 21) were excluded. Outcome Measures Utilization and yield of genetic testing, and diagnostic rate were assessed as outcome measures and compared to a baseline time period and a genetic testing protocol time period. Results There were 201 infants with CHD evaluated by the cardiogenetics program over 3 years. A total of patients 46 patients of the 196 who underwent genetic testing had multiple tests completed. This is a significant decrease from the baseline (247/329, P < .0001) and from the genetic testing protocol (29/81, P < .0387) time periods. The diagnostic rate was 33% which is significantly increased compared to the baseline rate of 15% (80/524, P < .0001) and trends toward a significant increase during the testing protocol rate (25/113, P = .0520). The number of dual diagnosis increased to 9 of 201 compared to the baseline (2/524) and the genetic testing protocol (1/113) time periods. The rate of incidental diagnoses altering care increased to 6 of 201 from the baseline (1/524) and the genetic testing protocol (1/113) time periods. Conclusion An inpatient cardiogenetics program significantly increases the diagnostic rate, the detection of complex phenotypes with dual diagnoses, the identification of incidental genetic diagnoses associated with changes in care, and significantly decreases the likelihood of multiple tests being completed on an individual patient. Increased medical geneticist involvement in programs that care for infants with CHD should be encouraged to improve patient care and genetic testing utilization.

Genetic Evaluation of Inpatient Neonatal and Infantile Congenital Heart Defects: New Findings and Review of the Literature

“…They emphasize that the involvement of a geneticist is critical [28]. The other studies of postnatal cohorts all reported higher yields than the 12% found in our study, with rates of 17% [37], 27% [39], and 36% [20]. In all of these studies, molecular testing was sent as second tier based on a geneticist's evaluation.…”

“…Some of the CHD infants who were not tested can be attributed to logistical issues related to test ordering and the realities of inpatient intensive care unit workflows. In addition to the current study, there have been two recent studies in infants with critical CHDs utilizing a comprehensive clinical algorithm for genetic testing with CMA [20,39]. In the study by Geddes et al, 98% of inpatient CHD infants underwent evaluation by a geneticist and genetic testing [20], whereas in the study by Skikany et al [39] and the current study, approximately 85-90% of patients underwent genetic testing.…”

“…At a previous institution, we reported yields of 21.7% for syndromic CHDs and 11% for isolated CHDs, but only a subset of patients had evaluation by a medical geneticist and therefore dysmorphic features were not included, potentially accounting for the differences in proportions between the two studies [39]. Another study, by Geddes et al, comprehensively evaluated and tested all inpatient infants with CHDs but did not specify extracardiac findings [20]. The testing yield for CNVs in that study was 22.6%, which is slightly higher than our overall yield of 14.6%.…”

“…Several studies, including prenatal studies, have previously demonstrated an increased diagnostic yield in the septal or atrioventricular canal classes of CHD [18,20,28,37,38] despite differing in their inclusion and exclusion criteria. In the current study, the highest yield occurred for septal and AVSD defects (20%), and this may either reflect characteristics of septal patients in the acute cardiac care setting (likely enriched for more medically complex septal cases) and/or the clinical algorithm that prioritized septal patients that had a priori suspicion for genetic diagnoses.…”

“…However, clinical genetic testing practices for CHDs vary significantly across institutions, and similarly, CMA may be inconsistently utilized as a first-tier test [16]. In addition, there have been limited studies of CMA investigations in clinical CHD cohorts, though more recent studies report overall diagnostic CMA yields of up to 14-24% depending on whether CHD is thought to be isolated or is seen in conjunction with dysmorphic features or extracardiac anomalies (ECAs) [17][18][19][20]. Differences in cohort ascertainment, type of genetic testing used, documentation of dysmorphology or other phenotypic features, and age of patient testing or evaluation make comparisons difficult.…”