What does a genetic syndrome associated CHD in comparison with CHD patients mean for clinical practice? A cross-sectional study by the German National Register for Congenital Heart defects
Authors: Remmele J , Helm P.C , Ewert P , Bauer U.M.M 
Published: November 2020

Abstract

Introduction
About 20% of all patients with congenital heart disease (CHD) showing other malformations and abnormalities. They have an increased likelihood for a genetic disorder which is either hereditary or firstly occurred spontaneously. Especially the influence of a genetic syndrome for clinical practice in CHD patients is of particular importance.

Purpose
This cross-sectional registry study focusses patients with CHD in comparison with patients having the most frequent genetic syndrome associated CHD, registered with the National Register for Congenital Heart Defects (NRCHD), to identify whether they are at higher risk for secondary diagnoses (SD), more surgeries and interventional treatments or not.

Methods
By using the NRCHD medical database at the date of 12 Feb 2020, out of a total of 55687 registered CHD patients, 34004 patients with CHD up to thirty years were identified. 28478 (female 48.1%; 16.1±7.0 years) CHD patients without any hereditary fetal or neonatal secondary diagnosis (HFN) representing the control group (CG) and 5526 (female 51.8%; 13.7±6.6 years) CHD patients with HFN were included in the statistical analyses. SD were defined and classified by using the International Paediatric and Congenital Cardiac Code (IPCCC). The CHD severity classification of Warnes at al. was used. Statistical analyses were conducted using a multinomial logistic regression model.

Results
Out of the 5526 CHD patients with HFN, the most frequent genetic syndromes associated with CHD were Trisomy 21 (1645 (4.8%); simple 300 moderate 974 complex 371), Catch 22-syndrome (306 (0.9%); simple 11 moderate 132 complex 163), Noonan syndrome (93 (0.3%); simple 13 moderate 71 complex 9) and Williams-Beuren syndrome (88 (0.3%); simple 2 moderate 82 complex 4). Regarding Trisomy 21 they have a significantly reduced risk of 26.8% for having a number of interventional treatments as high as the CG (OR:0.73 95% CI:0.60–0.89; p=0.002). In Catch 22-syndrome patients a higher risk for acquired secondary diagnosis 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) was found. A 28.6% higher risk for an increased number of extracardiac secondary diagnoses was shown in Noonan 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 a number of surgeries as high as the CG (OR:0.48 96%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).

Conclusions
Patients with genetic syndrome associated CHD could be assumed being at higher risk for secondary diagnosis, however, this holds true for Noonan syndrome and Catch 22-syndrome patients but not for patients with Trisomy 21 or Williams-Beuren syndrome. It would be necessary to monitor the genetic syndrome associated with CHD patients whether these findings change when they reaching older ages.

Funding Acknowledgement
Type of funding source: None