Congenital Heart Defects


CHD is a heterogeneous group of diseases characterized by teratogenic, Mendelian and chromosomal

abnormalities, with multifactorial origin, which one is born with. Certain teratogens, gene mutations,

environmental conditions, maternal age, diseases and some medications etc. can interfere with cardiac

signaling pathways and transcription factors and thus hinder normal development and cardiac

morphogenesis leading to CHDs.

Genetic and epidemiological studies suggest correlation of specific genotype with expression of particular cardiac phenotype and contribution by certain modifier genes in variable expressivity of these defects in genetic syndromes. There are several methods and techniques which can be made use of to facilitate research based studies of CHDs like copy number variation, DNA microarray, cytogenetic linkage analysis and whole exome sequencing.

Causes and risk factors

Some of the heart defects are caused by mutations of the individual chromosome or genes of the foetus.Many environmental and maternal factors also pose to be potent risk factors for CHDs in babies like mother’s diet, having rubella or health conditions like diabetes or obesity, use of medications like Zenatane or Claravis, smoking and alcohol consumption during pregnancy. Many of these defects are inheritable or associated with genetic syndromes like Down syndrome. Genetic factors like chromosomal anomalies contribute to about 15-30% of the cases.


CHDs can broadly be classified as:

Acyanotic- due to defect, atrial and ventricular septal defects, truncus arteriosus etc. and(b) Obstructive lesions as in pulmonary and aortic stenosis, coarctation of aorta etc.

Cyanotic- due to deoxygenated blood in circulation as in transposition of great arteries, Ebstein’s anomaly, tetralogy of Fallot, univentricular hearts, total anomalous pulmonary venous connection etc. which are more severe compared to the

acyanotic ones.

Scope of the defects

There has been a significant decrease in the mortality rate of infants post cardiac surgery due to

advancement in healthcare technologies like echocardiography and extensive use of prostaglandin for


The chances of survival of children with cardiac malformations has shown considerable increase due to adoption of primary repair at the stage of infancy itself but face problems like academic inattention or visual, behavioral abnormality and speech delay. The severity of the CHD, ranging from mild like septal defect to complex like univentricular heart, determines the degree of impairment in the patient.

Figure 2: schematic diagram representing milder forms of CHDs show high prevalence-low severity abnormalities but as complexity increases number of children with no disabilities considerably decreases. Image courtesy Cardiology in the Young vol. 16

Signs and symptoms

Some symptoms of severe heart defects include blue tint in skin, lips and nails, tiredness, poor blood

circulation, rapid breathing, arrhythmias and edema of body tissues which can be diagnosed and physically examined in special heart tests using echocardiogram, chest X-ray, pulse oximetry, cardiovascular magnetic resonance imaging (MRI) etc. Many CHDs do not show any specific symptoms and cannot be diagnosed until adulthood.

Treatment and future complications

Some heart defects like a small hole in the heart may heal on its own with age and safely go untreated but some are quite serious and need treatment as and when detected. Depending on type and severity of the defect as well as age and general health status of the child the treatment technique to be used is decided like using catheterization techniques, a heart transplant, open - heart surgery, drugs like angiotensin-converting enzyme (ACE) inhibitors and diuretics can help release stress on the heart. Even after treatment a child might still need lifelong monitoring and multiple surgeries, infection prevention and many exercise restrictions. It might even give some post-treatment complications like irregular heartbeat, heart stroke, hypertension, endocarditis or even sudden cardiac death.

Syndromic CHDs (genetic cause)

Sometimes chromosomal anomalies like Down, Edward, Patau, and Turner syndromes and certain

Mendelian disorders can affect patients with CHDs and are associated with a particular type of CHD as shown in tables below. Certain modifier genes like SLC2A3 can increase the risk of being born with CHDs.

Tables 1 and 2 give a list of many

syndromes found to be associated with cardiac anomalies and CHDs. New genomic conditions due to sub

chromosomal changes like deletion and amplification of DNA segment due to improper recombination and altered dosage of genes have also been identified which can produce new syndromic CHDs like duplication 22q11.2 syndrome, distal 22q11.2 deletion syndrome, Deletion 1p36 Syndrome and Microdeletion 1q21.1 and

the reciprocal micro duplication 1q21.1.

Image courtesy

Non-syndromic CHDs

These can be explained by multifactorial interaction of polygenic or single locus genetic predispositions with an environmental trigger. 5-10% of these can also be attributed to rare copy number variations like chromosome 8p23.1 having the GATA4 gene identified by gene mapping. Mendelian monogenic inheritance has also been found in few non-syndromic CHDs.

Neurological and developmental abnormalities associated with CHDs

Children with CHDs have increased chances of having structural anomalies of the brain like the congenital cerebral disease as there is simultaneous development of both the systems during gestation which can be altered by genetic factors. In addition to this, CHDs can reduce cerebral oxygen delivery and blood flow and can be detrimental to the CNS like microcephaly, underdeveloped operculum insulae, agenesis of the corpus callosum and periventricular leukomalacia leading to developmental delays. Also, severe CHDs need treatment and several preoperative (prostaglandin, ventilation etc.), intraoperative (hyperglycemia, hyperoxia etc.) and postoperative (extracorporeal membrane oxygenation and mechanical support) factors and certain genetic syndromes and environmental factors all pose to be potent contributors of risk to CNS.


CHDs are the most common birth defects which can be induced by genetic, environmental and maternal factors that can be critical and if left untreated can hamper normal functioning of the body and cause severe health issues and even death. Several diagnostic methods are being developed to detect new genes and chromosomal loci responsible for CHDs to identify causes of particularly syndromic CHDs. These heart defects lead to factors that lead to detrimental effects on CNS and neurodevelopmental anomalies which are major contributors of adverse life outcomes.

By Vidhi Sanghvi

Department of Biochemistry and Biotechnology

St. Xavier’s College


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