Rush Center for Congenital
and Structural Heart Disease





Embryology in clinical practice

Congenital heart disease is a result of abnormal cardiovascular development due to arrest or deviation of normal development.  Many etiological factors in precipitating specific congenital heart disease are well understood.  On the other hand, the inconsistency in outcome of specific etiological factors dictates that the cause of congenital heart disease is almost always multifactorial.  An example of this is complete atrioventricular canal defect in children with trisomy 21.  Almost 40% of children with Down syndrome are born with congenital heart disease.  There is a clear association of this chromosomal anomaly and the abnormal development of the heart, yet it cannot be the only factor since complete atrioventricular canal defect is not the only type of defect seen in trisomy 21 and not all children with this chromosomal anomaly exhibit congenital heart disease (tables 3&4).


Understanding congenital heart disease

Understanding the spatial relationship of complex structures is frequently difficult to explain or comprehend.  Cardiovascular embryology is specifically difficult to describe or illustrate due to its complex 3 dimensional nature and its continual changing as it develops throughout various embryological stages.  To make matters worse, educators and researchers continue to use mostly 2 dimensional still images.  The advances in computer illustrations and animations are making it possible to demonstrate with great effectiveness complex embryological developments of the heart through 3 dimensional animations.  Unfortunately, the process is cumbersome and costly.  Helpful animations, which could make the understanding of complex processes much easier to comprehend, are available through the internet:



Table 3

Syndromes associated with congenital heart disease


Associated congenital heart disease

Alagille syndrome

Peripheral pulmonary stenosis, tetralogy of Fallot

Beckwith-Wiedmann syndrome

Cardiomegaly, atrial and ventricular septal defects, truncus arteriosus

CATCH syndrome

Tetralogy of Fallot, ventricular septal defect, interrupted aortic arch, pulmonary atresia, truncus arteriosus

CHARGE syndrome

Tetralogy of Fallot, atrial, ventricular and atrioventricular septal defects, aortic arch anomalies, hypoplastic left heart syndrome, double aortic arch

Cornelia de Lange syndrome

Ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, patent ductus arteriosus, coarctation of the aorta

DiGeorge syndrome

Truncus arteriosus, double outlet right ventricle, tetralogy of Fallot, interrupted aortic arch

Down syndrome

Congenital heart disease is seen in 40% of patients, these include:  atrioventricular canal defect, ventricular septal defect, atrial septal defect, tetralogy of Fallot, patent ductus arteriosus. 

Glycogen storage disease

Hypertrophic cardiomyopathy

Holt-Oram syndrome

Atrial septal defect, less common ventricular septal defect, aortic stenosis, tetralogy of Fallot

Jervell-Lange-Nielson syndrome

Long Q-T interval, arrhythmia

Karatgener syndrome

Situs inversus, dextrocardia (mirror image situs).  Not associated with additional congenital heart disease.

Marfan Syndrome

Aortic root dilation, aortic dissection, mitral valve prolapse and regurgitation


Neurofibromata of the heart, renal artery stenosis, renal hypertension

Noonan syndrome

In 50% of cases:  pulmonary stenosis, conduction abnormalities (superior axis deviation), atrial septal defect, ventricular septal defect, tetralogy of Fallot, sub-aortic stenosis, complex congenital heart disease

Trisomy 13

80% of cases:  ventricular septal defect, patent ductus arteriosus, atrial septal defect, coarctation of aorta, dextrocardia, complex defects

Trisomy 18

ventricular septal defect, polyvalvar disease

Tuberous sclerosis Cardiac rhabdomyomas, Wolf-Parkinson-White syndrome
Turner syndrome

coarctation of aorta, bicuspid aortic valve, aortic dilatation, dissection and rupture
VACTREL syndrome Ventricular septal defect
Velo-cardio-facial syndrome Ventricular septal defect, tetralogy of Fallot, pulmonary atresia
Williams syndrome Thickening of media (muscular layer) of systemic and pulmonary arteries resulting in supravalvar aortic and pulmonary stenosis, peripheral pulmonary stenosis, coronary artery stenosis leading to myocardial infarction, cardiomyopathy and congestive heart failure



Table 4

Maternal conditions associated with congenital heart disease


Associated congenital heart disease

Fetal alcohol syndrome

ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of aorta

Fetal hydantoin syndrome

ventricular septal defect, tetralogy of Fallot, pulmonary stenosis, patent ductus arteriosus, atrial septal defect, coarctation of aorta

Fetal rubella syndrome

Pulmonary stenosis, peripheral pulmonary stenosis, patent ductus arteriosus

Fetal thalidomide syndrome

Ventricular septal defects, pulmonary stenosis, patent ductus arteriosus, conotruncal malformation

Fetal Warfarin syndrome

patent ductus arteriosus, peripheral pulmonary stenosis

Maternal systemic lupus erythematosus

Complete atrioventricular block, cardiomyopathy, l-transposition of the great vessels

Fetal rubella syndrome

Patent ductus arteriosus, peripheral pulmonary stenosis, ventricular septal defect, atrial septal defect, fibromuscular and intimal proliferation of medium and large arteries.

Maternal lithium ingestion

Ebsteinís malformation, Tricuspid atresia, atrial septal defect

Maternal diabetes

Transposition of the great vessels, ventricular septal defect, coarctation of aorta, Hypertrophic cardiomyopathy