The exact cause of
congenital heart disease is not known. Genetic factors have been implicated,
since children suffering from genetic disorders are more prone to develop heart disease
. Exposure of the mother to cigarette smoke
or other toxic substances could also predispose to heart disease in the baby.
‘Information on genetic mutations that cause congenital heart disease will help to identify the risk of the condition in successive generations’
identified several genetic mutations associated with congenital heart disease.
Genetic mutations are changes in the genetic material of an individual, which
is either passed on from the parent, in which case they are said to be
inherited, or occur for the first time in the individual, in which case they
are said to appear de novo
information was based on data obtained from 2871 patients with congenital heart
disease as well as their parents.
The genetic mutations that were found to be inherited by the children from
their parents included the following:
novo mutations :
in the FLT4 gene: This mutation
was associated with 2.3% cases of a complex heart disease called Tetralogy of Fallot. Tetralogy of
Fallot includes four heart defects namely, ventricular septal defect,
pulmonary stenosis, right ventricular hypertrophy and an overriding aorta
on the ventricular septal defect.
in the MYH6 gene: The MYH6 gene
encodes for a muscle protein called myosin. Mutations in the MYH6 genes have
been associated with 11% cases of Shone
syndrome. Shone syndrome consists of congenital defects affecting the
left side of the heart which include supravalvular mitral membrane,
parachute mitral valve, subaortic stenosis and coarctation of the aorta.
in the GDF1 gene: Mutations in
both the gene copies of the GDF1 gene were associated with around 5% cases
of severe congenital heart disease in children of Ashkenazian descent.
Mutations that were not inherited and appeared in the
genetic material of the affected children for the first time accounted for 8%
of the congenital heart disease cases. These mainly included those that affect
the chromatin, material in the nucleus. Among the patients with de novo
mutations, around 28% had both
neuro-developmental congenital abnormalities, and
abnormalities affecting organs besides the heart. Several of these genes have
been previously associated with autism.
The scientists also
found that twelve genes that were previously not associated with congenital
heart disease were found to have a more than 70% chances of association with
The new information will
help individuals identify the possible risk congenital heart disease in a
child. It will also help individuals to know the chances of a second child or
later generations suffering from congenital heart disease. Since a large number
of genes may be contributing to the congenital heart disease, the scientists
suggest that whole genome sequencing would be a better option than looking out
for a particular mutation.
Congenital Heart Diseases Congenital heart diseases
are heart defects present
since birth. They range from mild defects, which may go unnoticed until
adulthood, or serious defects which may be fatal at birth if left untreated.
Examples of congenital heart defects include atrial and ventricular septal
defects, narrow or incompetent valves, or complex defects like Tetralogy of
Fallot. The symptoms could include breathlessness, bluish discoloration and
fatigue. Heart murmurs may be noted on examination. The affected children can
suffer from long-term complications despite surgical treatment.
- Jin SC et al. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nature Genetics (2017) doi:10.1038/ng.3970
- What Are Congenital Heart Defects? - (https://www.nhlbi.nih.gov/health/health-topics/topics/chd)
- What Is Tetralogy of Fallot? - (https://www.nhlbi.nih.gov/health/health-topics/topics/tof)