What are the cardiac features of Down syndrome (Trisomy 21)?

From the Guidelines

Down syndrome is associated with several cardiac abnormalities, with congenital heart defects occurring in approximately 40-60% of affected individuals, and the most common cardiac features include atrioventricular septal defects (AVSD), ventricular septal defects (VSD), atrial septal defects (ASD), patent ductus arteriosus (PDA), and tetralogy of Fallot, as reported in the 2019 guidelines 1.

Cardiac Features of Down Syndrome

The cardiac defects associated with Down syndrome result from abnormal embryonic development of the heart, likely influenced by the genetic alterations associated with trisomy 21.

• Atrioventricular septal defects (AVSD) account for about 40% of heart defects in these patients, with most complete AVSDs occurring in Down syndrome patients, as noted in the 2008 guidelines 1.
• Ventricular septal defects (VSD) are also prevalent, affecting roughly 30% of those with cardiac involvement.
• Other significant cardiac abnormalities include atrial septal defects (ASD), patent ductus arteriosus (PDA), and tetralogy of Fallot.

Management and Follow-up

Early cardiac evaluation is essential for all infants with Down syndrome, typically including echocardiography within the first month of life, even in asymptomatic babies, as recommended in the 2010 guidelines 1.

• Management depends on the specific defect and may range from watchful waiting for small defects that might close spontaneously to surgical intervention for more complex abnormalities.
• Regular cardiac follow-up throughout life is recommended, as individuals with Down syndrome may also develop acquired heart problems such as mitral valve prolapse and aortic regurgitation in adolescence and adulthood, as highlighted in the 2019 guidelines 1.

Importance of Multimodality Imaging

The use of multimodality imaging, including echocardiography, cardiovascular computed tomography, and cardiovascular magnetic resonance, is crucial for the follow-up care of patients with congenital heart disease, as outlined in the 2020 appropriate use criteria 1.

• These imaging modalities help assess the severity of cardiac defects, monitor disease progression, and guide treatment decisions.
• Regular imaging studies can also detect potential complications, such as pulmonary hypertension, Eisenmenger syndrome, and cardiac arrhythmias, allowing for timely intervention and improved outcomes.

From the Research

Cardiac Features of Down's Syndrome

• Down's syndrome is frequently associated with complete atrioventricular septal defect, with a study finding that 71.6% of patients with complete atrioventricular septal defect had Down syndrome 2.
• Patients with Down syndrome and complete atrioventricular septal defect exhibited higher preoperative pulmonary artery pressure and resistance compared to patients without Down syndrome 2.
• Atrioventricular septal defects are more common in females with Down syndrome, with a study finding that females were almost twice as likely to have atrioventricular septal defects as males 3.
• Ethnic differences also exist, with blacks being more likely to have atrioventricular septal defects than whites, and Hispanics being less likely 3.
• Hypertrophic cardiomyopathy is also associated with Down syndrome, although it is less common, with only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome 4.
• Pulmonary vein stenosis is also a cardiac feature that can occur in individuals with Down syndrome, with a case report describing a neonate with Down syndrome who had atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis 4.
• The anatomy of the ventricles and the ventricular component of the atrioventricular septal defect can differ between individuals with and without Down syndrome, with outlet extension of the ventricular component of the defect being more common in individuals with Down syndrome 5.
• Genetic factors, including the Notch pathway and genes involved in the ciliome, may contribute to the increased risk of congenital heart defects in individuals with Down syndrome 6.
• A polygenic component may also contribute to the risk of atrioventricular septal defects in individuals with Down syndrome, with a study finding that polygenic risk scores were associated with an increased risk of atrioventricular septal defects 6.