What do we know about the genetics of HLHS?

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Oct 3, 2017 | Suzanne Ferguson | @suzannerferguson

One of the main goals of The Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) is to find the genetic cause of the congenital heart disease (CHD). Here’s what we know so far:

There is no single gene that causes HLHS. There are many unique genes that are important during heart development and it is possible that a genetic variant in any one of those genes would be enough to lead to HLHS. While variants in specific genes have been linked to HLHS, they are identified in a very small subset of individuals.

The genetics of HLHS is complex. While there isn’t a single gene that causes HLHS, the same genetic variant may cause many different types of CHD. In fact, multiple studies have shown a strong familial clustering of HLHS with other CHDs. The big question as to why a single genetic variant may cause HLHS in one patient and a bicuspid aortic valve in their sibling is unknown and may be due to other genetic variants or possible environmental factors.

It gets even more perplexing. The term incomplete penetrance in genetics means that an individual may carry the same variant thought to cause HLHS in one family member but that same individual does not have any sort of CHD. While there may be a variant that drives HLHS during the early stages of heart development, there are likely other factors involved in the occurrence of this complex trait.

That’s why our HLHS program sequences the entire genome of all study participants (individuals with HLHS, mothers, fathers, siblings and any additional family members known to have a CHD).  It is our goal to fully understand the genetics picture to find better ways to provide solutions for HLHS. To learn more or to participate in the research program, email HLHS@mayo.edu.

The Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) is a collaborative network of specialists bonded by the vision of delaying or preventing heart failure for individuals affected by congenital heart defects including HLHS. The specialized team is addressing the various aspects of these defects by using research and clinical strategies ranging from basic science to diagnostic imaging to regenerative therapies.