Genetic testing for heart conduction

Genetic testing for heart conditions is a huge growth area

by crustyg - 2021-08-12 19:07:19

I hope that the results are successful: there's a least one contributor here whose diagnosis of Brugada was initially missed.

I don't know much about the genetics of HB (as opposed to channel defects causing problems like Long-QT or Brugada): what are they looking for?

There's increasing evidence that some cardiac disorders (thinking HCM/DCM) have complex inheritance.  Anyone else in your generation or older with comparable symptoms?

Genetic testing

by Julros - 2021-08-12 20:22:39

My 40 year old son was tested after he pushed for answers about the cause of aflutter/afib. He was found to have a LMNA defect, which leads to bradyarrhythmias and dilated cardiomyopathy. He had a pacer/icd placed shortly after. I was found to have a flutter 2 years ago, after having a small stroke. Now my sister has it, and we had a grandmother who died of a stroke in her 50s. I plan to ask my new EP about this at visit next month. 

curious question

by dwelch - 2021-08-13 11:13:59

So I have CCHB and my understanding thus far is that it comes from an auto-immune issue in the mother during pregnancy.  And thus not hereditary.  Is this still the understanding?  

Does this question associated with HB from birth or just in general that at some point HB will happen at some point later in life and if that is detectable?

When I asked this question to the docs when it was a concern, mine was not hereditary so there was no test.

Good question in general if there are tests for any heart condition that happen before you find out the hard way.  I hope there is good news here.

SLE in mother during pregnancy is a common cause of CCHB

by crustyg - 2021-08-13 12:08:00

Overwhelmingly, acquired CHB is caused by ischaemic heart disease, but there are plenty of genetic heart conditions that can produce conduction issues including CHB.  However most/nearly all of these have some additional cardiac or non-cardiac associated impairment.

Just had an online education session about the genetics of HCM/DCM and it was, for me, bewilderingly complex.  And that was just for the cardiomyopathies (which can also have an acquired conduction problem/CHB).  Part of the challenge is that even with increases in the number of genes being tested for in each panel, diagnostic yield has stuck at about 30% over the last 25yrs - and that's from populations of patients who 'obviously' have significant cardiac disease, not just HB.  A small part of the challenge is that some abnormalities were not recognised as disease-causing as recently as 10years ago, more seriously labs weren't looking for deep intronic variants (i.e. not sequencing very far into the non-coding introns between the protein-coding gene segments (the exons)).  Experience with sequencing for cystic fibrosis has shown that deep-intronic analysis is essential for this disease to be reliably detected.

More worrying is the suspicion that *some* patients may have clinical disease because of subtle interactions between genetic variations that are not classified individually as disease-causing, but which occuring together in one person lead to problems.  And that's a nightmare to track down.  Usually a family history and genetic analysis of other family members is a powerful way to identify different (i.e. not of normal sequence) genes that are indeed disease causing by showing that these different genes track in the family and fit with who has disease (not always very severe).

At the moment, we're fairly wedded to the idea that a one abnormal copy of a gene, or perhaps two abnormal copies leads to disease.  Relatively few cases are diagnosed where a single copy of a duff gene at <a> and a single copy of a duff gene at <b> is considered to be the cause of a disease.  I'm specifically exempting a simultaneous mitochondrial problem here - add that in and all bets are off.

Which I *suspect* is why we're decades away from understanding who will get SSS from over exercise without IHD. IMHO, there is/will be proven to be a genetic component, but it won't be easy to tease out.

Ditto for acquired HB with no clear evidence of other cardiac disease.

But that's only my personal speculation.  It's a huge and rapidly expanding area.  Even though a genetic analysis panel is now relatively cheap (about $1000), this is more than most healthcare systems/providers will spring for without a good reason, or belief that the results will change patient management.  However, the better labs keep the data from these DNA samples and can then review them, perhaps 10years later, looking for things previously disregarded.  Some labs even keep the DNA itself for more than 5years to permit this type of retrospective research.

One of the big research hospitals raided their long time (30+years) store of frozen patient samples after Legionnaire's disease was first reported and showed that a significant number of 'pneumonia' patients from yesteryear did in fact have that infection.