No specific causes are found in most cases of congenital malformations of the heart. In a minority cases, clear-cut single causes, either environmental or genetic, are responsible. No good evidence is available implicating interaction of specific genetic and exogenous factors in the causation of cardiac malformation in man, though experiments on animals suggest such an interaction.

Inheritance
A few families are reported in which defect follows dominant pattern of inheritance, e.g. atrial septal defect, supravalvular aortic stenosis, cardiomyopathy. Recessive autosomal inheritance confined to heart is exceptional.

Chromosomal Abnormalities
About 5 percent of patients with congenital heart disease are associated with some chromosomal abnormalities (Table 1).

Table 1: Incidence of Congenital Heart Disease with chromosomal abnormalities

Chromosome abnormality	Name of syndrome	Incidence of CHD (percentage)	Type of defect
21 Trisomy	Down's syndrome	60	A-V canal defect VSD
18 Trisomy	-	90	VSD, PDA, DORV
13 Trisomy	-	90	Dextrocardia, VSD, PDA
XO	Turner's syndrome	15	Coarctation of aorta, aortic stenosis

Environmental Factors
Increased incidence of congenital heart defect has been noted with intrauterine viral infections, maternal drug consumption during first trimester of pregnancy and pregnancy-induced systemic maternal diseases. (Table 2)

Table 2: Incidence of Congenital Heart Disease with environmental factors.

Environmental factors of Cardiovascular Malformation
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Maternal Infections
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• Rubella: PDA, pulmonary stenosis,VSD, ASD
  
  
• Mumps: Endocardial Fibroelastosis
  
  

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Maternal Drugs
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• Phenytoin: Variable
  
  
• Vitamin D: Supravalvular aortic stenosis
  
  

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Maternal Disease
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• Diabetes: Transposition of great arteries
  
  
• Systemic Lupus Erythematosus: Congenital Heart Block
  
  

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Multifactorial Causation
The most acceptable theory for the genetic basis of congenital heart disease is multifactorial hypothesis. It suggests that the abnormalities of genes may not be enough to cause cardiac malformations, but may manifest in presence of above mentioned adverse environmental hazards.