What Is the Role of Genetic Syndromes in Clinical Practice for Patients with Congenital Heart Defect?

Objectives: Patients with congenital heart disease (CHD) show other malformations and abnormalities in approximately 20%. They have an increased likelihood of a genetic disorder that is hereditary or occurred spontaneously. The influence of a genetic syndrome for patients with CHD is of particular importance. This study focuses patients with CHD in comparison with patients having genetic syndrome associated CHD to identify whether they are at higher risk for secondary diagnoses (SD), more surgeries, and interventional treatments or not.

Methods: A total of 34,004 patients with CHD up to 30 years were identified using the NRCHD medical database. Overall, 28,478 (female 48.1%; 16.1 ± 7.0 years) CHD patients without any hereditary fetal or neonatal secondary diagnosis (HFN-SD) representing the control group (CG) and 5,526 (female 51.8%; 13.7 ± 6.6 years) CHD patients with HFN-SD were included in the statistical analyses. HFN-SD class is the International Pediatric and Congenital Cardiac Code (IPCCC) and CHD severity class is defined by Warnes et al (simple [S], moderate [M], and complex [C]).

Result: Out of the 5,526 CHD patients with HFN-SD, 2,132 having the most frequent genetic syndromes associated with CHD. Trisomy21 (1,645 [4.8%]; S: 300; M: 974; and C: 371), DiGeorge's syndrome (306 [0.9%]; S: 11; M: 132; and C: 163), Noonan's syndrome (93 [0.3%]; S: 13; M: 71; and C: 9) and Williams–Beuren syndrome (88 [0.3%]; S: 2; M: 82; and C: 4). Trisomy21 patients have a significantly reduced risk of 26.8% for having several interventional treatments as high as the CG (OR: 0.73, 95% CI: 0.60–0.89; p = 0.002). DiGeorge's syndrome patients are at higher risk for acquired SD of 17.6% (OR: 1.17, 95% CI: 1.05–1.31; p = 0.004), as well as for interventional treatments of 6.9% (OR: 1.06, 95% CI: 1.01–1.14; p = 0.033). A 28.6% higher risk for an increased number of extracardiac SD was shown in Noonan's syndrome patients (OR: 1.29, 95% CI: 1.06–1.56; p = 0.010). Patients with Williams–Beuren syndrome are at 52.1% decreased risk for having several surgeries as high as the CG (OR: 0.48, 95% CI: 0.28–0.83; p = 0.008) but a higher risk for a higher number of interventional treatments of 20.5% (OR: 1.21, 95% CI: 1.06–1.37; p = 0.004).

Conclusion: Patients with Noonan's syndrome and patients with DiGeorge's syndrome confirm the assumption that they have to deal with more secondary diseases even in younger ages, but not patients with Trisomy21 or with Williams–Beuren syndrome. It would be necessary to monitor CHD patients with syndromes whether these findings change when they reaching older ages.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
21 February 2021