Congenital heart disease, a heart problem that develops before you are born, is the most common condition people are born with. It may involve abnormal connections between the chambers of the heart, narrowing of structures in the heart or blood vessels through which blood should normally flow freely, or sometimes part of the heart fails to form entirely. In most cases, it happens because something has gone wrong during the crucial stages of heart development, around two months into pregnancy. The reasons why this happens are still not fully understood, but sometimes your genes can play a role. Unlocking the secrets of how genes influence the development of heart and blood vessels could help to treat congenital heart problems, as well as identifying which families are at risk and could benefit from specialist advice.
BHF Professor Bernard Keavney at the University of Manchester has identified “mistakes” in genes that contribute to heart problems at birth. In some cases, these can run in families, but often the genes causing the problem are unknown. With BHF support, Professor Keavney’s team is screening the entire DNA – or genome - of people with congenital heart disease and their parents to find possible causes. In 2012, Professor Keavney and his team showed the importance of tiny genetic changes in causing congenital heart disease, and showed these may explain up to 10 per cent of cases. Screening for these genetic ‘mistakes’ is now part of the assessment of some babies and children with congenital heart disease.
In 2013, the team carried out the world’s first genome-wide association study in people with congenital heart disease. This kind of study involves looking at a group of people with a condition, scanning their entire DNA to find genetic changes which they have in common, and working out if these genetic changes are responsible for the condition. The study discovered a gene which causes atrial septal defect (hole in the heart) - one of the most common congenital conditions – and is thought to be responsible for about one in 10 of cases.
In 2019, Professor Keavney and his team identified the most important genes linked to a complex condition called tetralogy of Fallot. It’s among the most common serious congenital conditions, and in eight out of 10 cases, we do not know the cause. The study showed that the changes in two specific genes are present in up to one in 10 people with tetralogy of Fallot. This study has contributed the best information we have so far about the genetic causes of tetralogy of Fallot.
Understanding the genetic causes of congenital heart disease could help us understand more about how the condition can be passed on through families, and provide better advice and counselling to high-risk families as well as finding new treatments which one day could prevent the heart developing abnormally.
22q11.2DS syndrome (also known as DiGeorge Syndrome) is a condition you are born with, which can cause a varied range of lifelong problems, including heart defects. Supported by the BHF, Professor Peter Scambler and his team at the Institute of Child Health in London found in the early 1990s that a small deletion on a specific region of chromosome 22 (called 22q11.2) was the most frequent cause of the condition. The team went on to discover which gene is involved in causing the syndrome. Recently, his research has focused on understanding how this gene, and other genes that can be affected by this gene, are important for the correct development of the embryo in its early stages.
For some children, 22q11.2DS syndrome can cause severe problems, but many others grow up without realising they have it, potentially passing it on to their children. So it’s useful to be able to test for the gene that causes the syndrome.
Thanks to the work to discover the genetic causes of 22q11.2DS syndrome, we now have a genetic diagnostic test, which can be offered to people who have cases of 22q11.2DS syndrome in their family when they are planning to have a child. It is available in several NHS genetic diagnostic screening centres across the UK. As well as giving potential parents the best information, it also helps doctors to confirm or rule out the diagnosis in a child, and so enable them to provide the best care.
First published 1st June 2021
Scientists at the University of Manchester have published BHF funded research showing possible genetic causes of congenital heart condition, Tetralogy of Fallot (ToF).
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