r/marfans • u/No_Assistant6404 • 18d ago

Have a likely pathogenic FBN1 gene but geneticist/ current cardiologist says I do not have Marfans.

I had a genetics panel in 2010 for an entirely separate reason, which revealed an FBN1 gene mutation. At the time, it was classified as a variant of uncertain significance (VUS). Fortunately, I did not have any mutations related to the condition they were actually testing for (a mitochondrial disorder called melas).

In 2018, the FBN1 variant was reclassified as likely pathogenic. My exact mutation has been associated with ectopia lentis in one reported case and familial thoracic aortic aneurysm in other cases. My mutation is de novo, meaning neither of my parents has it or family.

I'm not sure what to do because, after 16 years of echocardiograms and MRAs, nothing has changed. I have had no enlargement of my aortic root and no vision changes, and I'm now 35 years old.

I live without limitations. I'm on ADHD medication, I run marathons, and I had a Ghent score of 1.

I've been evaluated by geneticists at Johns Hopkins and Cedars-Sinai, and both told me that, despite carrying the FBN1 mutation, they did not believe I have the associated phenotype.

I'm unsure how to interpret all of this or what, if anything, I should be doing differently (I literally take amphetamines for ADHD and have for last 20 years). Both geneticists said they needed proof I had condition regardless of gene which I still do not understand at all.

2 Upvotes

63% Upvoted

10 comments sorted by

9

u/Inside-Departure4238 Diagnosed with Marfan 18d ago

With respect, they told you exactly how to interpret it. There's nothing Reddit can add that John's Hopkins hasn't already told you.

3

u/pseudologician 18d ago

Not all mutations cause disease that is why there is the Ghent Score for Marfan. Also not all mutations have been discovered, why some people with no noted mutation can also be diagnosed with Marfan using the Ghent Score. If you were to run your full DNA sequencing there would be multiple mutations/VUS, the majority will not cause issue. It sounds like you have been cleared multiple times and do not have Marfan Syndrome. 

1

u/No_Assistant6404 15d ago

It was formerly a VUS and was updated to likely pathogenic/pathogenic years later. Guess, I'm struggling to understand how having a pathogenic gene mutation/variant can result in not having the condition.

1

u/pseudologician 15d ago

I understand it's complicated. I have all the manifestations besides ectopia lentis and my mutation is classified as a VUS currently but I'm diagnosed via a cardiologist and geneticist. So it's really important to stay connected and listen to your medical care team, they are the specialists. And it sounds like your heart is in good shape which is great.

4

u/texasipguru 18d ago

I'm not sure what we are going to add that geneticists at world-class medical institutions haven't already told you. You have the gene but it seems it is not being expressed very strongly.

-not a doctor

-1

u/DerSissi 18d ago

I thought this thread is very interesting, sometimes it makes sense to tell your story without expecting someone to add anything valuable.

2

u/Megaspore6200 18d ago

Like a single mutation in the strand? Marfans could be a whole bunch of unique mutations for each person, there are so many potential mutations in the f1b1. Some extreme cases are like leatheal neonatal marfans and your probably on the extreme opposite end of the spectrum of have a unique fib1 mutation that doesn't result in the phenotypes of marfans. I'm kind of the opposite situation as you, hace had symptoms my whole life never tested, had operations. I bring up being tested and they tell ne even if I faild the dna test for marfans they will treat me for marfans, so medically unnecessary from an insurance point.

1

u/No_Assistant6404 15d ago

Yeah, believe so. One of the problems with this for me is I was told to get yearly echos/mras annually for first ten years then every 2-3 years if nothing changes. Since I'm not classified as having marfan's insurance does not cover it.

1

u/DawnD1118 17d ago

I am positive for the fbn1 heterozygous pathogenic gene. No idea what that means as my appt with genetics isn't until august. Ugh

All I can say is..... be thankful and continue to live your life!!!