Genetics and heart conditions

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Learn about the role that genetics plays in many heart conditions that afflict children.

Key points

  • Spontaneous genetic changes in the body, genetic mutations, and external or environmental influences can all result in a congenital heart condition.
  • Heart conditions can be a part of a genetic disorder or syndrome.

Congenital heart conditions can have many causes. In fact, the same condition in two different children could have completely different origins. Congenital heart conditions may be the result of spontaneous genetic changes in the body, genetic mutations that are inherited by a child from a parent, changes caused by external or environmental influences, or a combination of these factors.

Genetic disorders can result in isolated heart conditions or heart conditions within the context of a syndrome that affects the body and its organs and functions in different ways. In some cases, a heart condition may be the first clue that a patient has a syndrome. As a result, children with heart conditions should be assessed to see whether their heart condition is just one part of a syndrome.

This page gives examples of some specific genetic disorders and syndromes that can result in heart conditions. In some cases, syndromes are discussed in more detail in the section on Understanding Diagnosis. For more detailed information, please consult your doctor or a genetic counsellor.

Chromosomal disorders

Chromosomal problems, such as duplication or deletion, are at the root of conditions like Down syndrome, Turner syndrome, Williams syndrome, and 22q11.2 deletion syndrome.

Down syndrome

Down syndrome is caused by an additional copy of chromosome 21. This means that instead of the normal pair of chromosomes, there are 3 copies. This is called a trisomy. Down syndrome is also referred to as Trisomy 21. A trisomy is caused by an error that occurs during cell division. The most commonly associated congenital heart defects in Down syndrome are atrioventricular septal defect, tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus.

Turner syndrome

Turner syndrome, which affects only females, occurs when one of the pair of sex chromosomes (X chromosomes) is missing or partially missing. It can result in coarctation of the aorta in the 10% to 15% of patients who have cardiac problems.

22q11.2 deletion syndrome

A number of syndromes that can affect the heart, including DiGeorge syndrome and velocardiofacial syndrome, are caused by a deletion in chromosome 22 (22q11 deletion). The heart conditions most commonly seen are interrupted aortic arch, tetralogy of Fallot, pulmonary stenosis, and certain septal defects.

Williams syndrome

Williams syndrome is caused by a deletion in chromosome 7. Heart conditions are seen in about 80% of patients with supravalvular aortic stenosis and other lesions caused by the narrowing of muscular vessels being the most common. Atrial septal defect is seen less commonly.

Single gene disorders

Single gene disorders result in several conditions that affect the heart. Examples include Marfan syndrome, familial high cholesterol, Friedreichs ataxia, Ellis-van Creveld, and Holt-Oram syndrome.

Marfan syndrome

Marfan syndrome is caused by a mutation of a gene on chromosome 15. This gene controls the making of a protein (fibrillin) necessary for connective tissue. Most causes of Marfan are inherited, but some cases occur as the result of a spontaneous mutation. If one parent has the syndrome, there is a 50% chance that a child will have it. Marfan syndrome can affect many organs, including the skeleton, lungs, and eyes, as well as the heart and blood vessels. Connective tissue is weakened in this condition. It can result in heart conditions such as aortic regurgitation, aortic dissection, and mitral valve prolapse.

Familial high cholesterol

Cholesterol is a fat found in the blood. Familial high cholesterol, also called familial hypercholesterolemia, is caused by a mutation in the gene that controls the making of a protein that removes cholesterol from the blood. As a result, there is too much cholesterol in the blood.

Too much cholesterol can lead to hardening of the arteries (atherosclerosis) and early heart attacks. If one parent has the condition, a child has a 50% chance of inheriting the disorder.

Friedreichs ataxia

Friedreichs ataxia is caused by a defect in a gene that is responsible for the creation of a protein needed by the brain, nerves, heart, and other organs. If both parents have one copy of this mutation, a child has a 25% chance of inheriting the disorder. Signs of the condition occur during childhood, beginning with difficulty walking (ataxia). The condition then gets worse, with signs and symptoms that include muscle weakness and speech problems. Heart disorders that can occur with this condition include cardiomyopathy and arrhythmias.

Ellis-van Creveld

Ellis-van Creveld, also known as chrondroectodermal dysplasia, is caused by a mutation in a gene on chromosome 4. The signs of the syndrome include dwarfism, extra fingers and toes, dental problems, and heart conditions, most commonly atrial septal defect. If both parents have a single copy of this mutation, a child has a 25% chance of inheriting the disorder.

Holt-Oram syndrome

Holt-Oram syndrome, which is also called heart-hand syndrome, causes abnormalities of the upper limbs and heart. The most common cardiac problems associated with this syndrome are atrial septal defect and ventricular septal defect.

Tuberous sclerosis

Tuberous sclerosis is a complex condition that affects the skin, brain, kidney, and heart. Abnormal growths of heart muscle, called rhabdomyosarcomas, may interfere with the flow of blood through the heart. Abnormal heart rate rhythms may also occur. Mutations in one of two genes, TSC1 and TSC2, have been pinpointed as the cause of tuberous sclerosis. About two-thirds of the mutations arise spontaneously, however there is a 50% chance that a child will inherit the abnormal gene from an affected individual parent.

LEOPARD syndrome

LEOPARD syndrome is a rare condition affecting growth, the heart, and the brain. Narrowing of the pulmonary valve, obstructive cardiomyopathy, and conduction abnormalities occur in this condition. A mutation in the PTPN11 gene is responsible for LEOPARD syndrome.

CHARGE association/syndrome

CHARGE association/syndrome describes a pattern of congenital anomalies that affects several organ systems, including the eye, ear, nose, and heart, as well as the gastrointestinal and genitourinary areas. The acronym stands for the following:

  • Coloboma, a keyhole-shaped notch in the iris of the eye
  • Heart defects, such as atrial septal defect, ventricular septal defect, and tetralogy of Fallot
  • Atresia of the choanae, which is a narrowing of the passages in the nose
  • Retardation of growth and development
  • Genital and urinary problems
  • Ear abnormalities and/or hearing loss

CHARGE almost always occurs sporadically, which means there is not a family history of CHARGE. The chance of another child in the family having CHARGE is 1% to 2%; however, the person with CHARGE may have a higher risk of having affected children.

Alagille syndrome

Alagille syndrome is marked by a lack of bile ducts in the liver. About 90% of patients with this condition also have a heart condition. This is most often peripheral pulmonary stenosis and tetralogy of Fallot, and less commonly ventricular septal defect, atrial septal defect, aortic stenosis, and coarctation of the aorta.

Multifactorial disorders

A number of congenital heart defects, when isolated or not part of a syndrome, are thought to be multifactorial disorders, along with conditions such as clubfoot, cleft palate, and diabetes.

VATER/VACTERL association/syndrome encompasses characteristics that occur together, like CHARGE. The acronym describes the association of the following anomalies:

  • Vertebral anomalies
  • Anal atresia
  • Cardiovascular anomalies
  • Tracheoesophageal fistula
  • Esophageal atresia
  • Renal (kidney) anomalies
  • Limb anomalies

The most common heart defects seen with VACTERL association are ventricular septal defects, atrial septal defects, and tetralogy of Fallot. Less common defects are truncus arteriosus and transposition of the great arteries. The cause of this condition is considered to be multifactorial, since no specific genetic or chromosome problem has been identified.

Mitochondrial disorders

Mitochondrial disorders occur when the mitochondria fail and are not able to produce the energy a cell or tissue needs. These disorders appear to cause most damage to the brain, heart, liver, skeletal muscles, and kidney, which are tissues with the highest demands for energy. Mitochondrial disorders most often present as muscle weakness with neurological problems; other symptoms include poor growth, heart failure due to cardiomyopathy, gastrointestinal disorders, liver disease, and diabetes.

Last updated: December 4th 2009