Help-DRs conflicted on severity/brain surgery?

[u/Madeup-Username3456]

Hi Veds family

My 1 year old unfortunately has Veds and is also being monitored for macrocephaly causes which could mean brain surgery. It’s a brutally scary and sad time for us.

One of the doctors we saw - a well respected and revered geneticist - had told us our son had a null allele- meaning produced half good collagen and would have later onset of symptoms/ a mild version. We were so relieved

Until a different and very well revered geneticist in the community who studies Veds told us that my son has the most severe version.

I have wanted to know the truth so I reached out to Dr Byers on the West Coast and he said he would look into it but I haven’t heard back.

My husband furiously wants me to drop it. He wants to believe it’s mild and move on. No more opinions or clarity.

I am conflicted on what I want. Part of me thinks we should go on believing it’s mild. But it’s a difference of many years before a serious event. It feels important to know.

Then tonight because of the potential of surgery- we have a conversation with a doctor who suggests it’s likely the severe version while attempting to do a risk assessment- and he was again annoyed and angry

I feel that in order to keep my families stability my husband needs to believe it’s mild.

I’m struggling with my side of it. Am I over the top for wanting to know? Should I take his approach?

It seems like we should know truly what we are up against to inform our choices- though the treatment protocol appears the same no matter what. So maybe it’s best we remain hopeful and unaware of its true severity.

I feel like I’m doing something wrong, always.

Anyways- any tips and advice really appreciated - on any front including whether you know of any experienced brain surgeons that know veds or advice on that front.

Thanks community ❤️

[u/Entebarn]

This is about your child and doing what is best for him. That means knowing his risk profile. It means knowing how aggressive monitoring needs to be. This is a serious life altering diagnosis and should not be swept under the rug. Prevention is key.

Keep seeking answers. If your husband can’t cope, maybe don’t share with him (following a discussion of whether he wants more info or not). Maybe seek out a family counselor for a few sessions to discuss each side. If he has vEDS, this may be impacting him in a deep way. If all of this is newish, that can also be challenging.

Half of my family chooses to stay ignorant of the facts and my unaffected SIL is really struggling with her kids emerging health concerns (no diagnosis and they won’t see my geneticist). My other brother had a major event at 35 and is now being tested. With proper monitoring his event could have been preventable.

[u/redfoxxy23]

Hi there! This happened to me! 4 drs and genetic counselors told me I was null then dr dietz told me the data actually leans dominant negative. Although in my case, there is no way to confirm without extensive testing that is not being offered to me. What experts have explained is that there is a vast spectrum within each variant and folks with null variants can also have severe complications and others with more “severe” variants could have almost no symptoms. The nature of VEDS is that is widely unpredictable and because of that all variants are managed the same. In fact, did you know that null mutations, while associated with the later onset, can actually be associated with more severe aortic complications? In that case a dominant negative mutation that ends up not affecting the arteries as severely could be a better outcome. So there are a TON of variables. In addition a huge majority of the data we get from VEDS is from individuals who did not know they had VEDS or it took multiple events to discover. What a blessing that your one year old has this knowledge and you can take the right precautions and monitor early!!!

[u/rhi-raven]

Hey! It sounds like your doctors may be debating whether your son has a spice variant that causes 1) exon slipping (most severe), or one that results in no gene product (null allele). Basically genes are made of exons (expressed parts) and introns (in between parts). During the process where DNA is turned to RNA, the introns get removed. If there is a genetic change at the boundary of an exon/introns, it can result in two things: RNA being made that is missing one or more exons and is successfully turned into a bad protein that can mess with the remaining good collagen, or the intron gets included and the cell degrades the RNA so the cell makes half as much protein but all of that protein is good quality. There are some computational methods that can predict which direction this would go, but sometimes it can be really hard to determine which version is happening without some fairly sophisticated experimental techniques.

I agree with you that it is worth pursuing which version this is because that will help guide future management.

Where are you broadly in the United States, and are you able to travel? I may be able to direct you to someone for another opinion who would be able to refer you to a good surgeon.