This is part two of my post on dissecting (pun intended!) the new diagnostic criteria for Marfan syndrome. You can access part one, which discusses the reasons behind the updated criteria, here. I was going to put the new criteria for related disorders in this post as well, but then I realized this post is already too long. So, look for the final part on Monday. The National Marfan Foundation has put together information on the new criteria. And as a reminder: I am not a doctor, I’m just trying to translate the scientific jargon into an easier to understand format. Any specific questions you have about the new criteria can be directed to Amy Kaplan, RN, at the NMF: akaplan@marfan.org or your doctor.

The biggest change behind the new criteria is that it basically redefines Marfan syndrome such that aortic involvement (or the defined potential for aortic involvement) MUST exist. Previous to this, we’d said about 20% of Marfan patients don’t have aortic aneurysms. I’d assume that now that percentage is much smaller.

Before I outline the new criteria, you need to understand what a z-score is. Aortic sizes are plotted on a chart based on age, body size, and the aortic root size at the sinuses of valsalva. This chart will show you where your root fits in the realm of what is considered normal for a person of your age and size. Mark could give you some big explanation on statistics, but the Maya-version is that the z-score takes those different sizes of aorta and groups them. A score of 2 and over (meaning 2+ deviations from normal) is significant in the terms of diagnosing Marfan. That means the aorta is enlarged. Follow me?

You’ll also hear about the systemic score. There are 20 possible points and the features are the skeletal symptoms that made up the former “skeletal criteria,” as well as dural ectasia (it’s been downgraded; no longer its own category), myopia, and pneumothorax. Symptoms that have been shown through research to be tied closely with Marfan are given more points, like being able to do both the thumb and wrist sign (3 points), and those that occur frequently in the general population, like mitral valve prolapse (1 point) have been given less importance.

Finally, there are two types of FBN1 mutations. A small amount (I’ve been told about 12%) are known to cause aortic aneurysms. These are mutations that overlap among unrelated families. The majority of people who test positive for an FBN1 mutation have a mutation that is unique to their family. These are considered mutations not known to cause aortic aneurysms, because they are brand-new mutations. Make sense?

So, if you’re someone without family history of Marfan (like me), you need to meet one of the following scenarios to get a positive diagnosis:
1) A z-score of 2 or more and ectopia lentis (dislocated lenses)
2) A z-score of 2 or more and a mutation found on FBN1
3) A z-score of 2 or more and 7 points or more in the systemic score
4) Ectopia lentis and have a mutation found on FBN1 that is known to cause aortic aneurysms
5) This one is not something I understood from reading the paper, but Dr. Dietz confirmed it with me and since he WROTE the paper, I figure he’s right so I’m adding it: A mutation in FBN1 that is known to cause aortic aneurysms and 7 or more points in the systemic score.

Other possible diagnoses:
1) Ectopia lentis with or without systemic involvement and either no FBN1 mutation or one that hasn’t been identified with aortic aneurysms = a diagnosis of Ectopia Lentis syndrome.
2) A z-score of less than 2 and a systemic score of at least 5 (as long as it includes at least one skeletal feature) and no ectopia lentis = a diagnosis of MASS
3) Mitral valve prolapse and a z-score of less than 2 and a systemic score of less than 5 with no ectopia lentis = a diagnosis of Mitral Valve Prolapse syndrome

If you’re someone with a family history of Marfan, you need to meet one of the following scenarios to get a positive diagnosis:
1) Ectopia lentis and a family history of Marfan syndrome (as defined by above)
2) Systemic score of at least 7 and a family history of Marfan
3) A z-score of 2+ if you are at least 20 years old and a z-score of at least 3 if below 20 years old and a family history of Marfan

One thing to consider is that for some of these scenarios, doctors must first rule out features of related disorders. This is true for scenarios 1 and 3 of not having family history and scenario 2 of having family history.

I’m going to cover the features of the many related disorders on Monday. There is one very important thing to remember: the whole point of this is to ensure that people are being followed appropriately. The authors acknowledge that someone with a MASS diagnosis could, at some point, develop an aneurysm and therefore qualify for a Marfan diagnosis. Therefore, even if your diagnosis has changed you should still get at least periodic echocardiograms.

For a short time, before I talked with Dr. Dietz at conference, I thought my diagnosis of Marfan syndrome had been taken away by this new paper. I was devastated and spent several days freaking out about what this meant (my diagnosis, for those who don’t know, has flip-flopped 3 times over the course of the past 17 years and it’s stressful and sucks and I was not ready for it to happen again). I’m glad to know that I do, in fact, still fit in the Marfan box, but I realize that not all of my friends do any longer. I just want to reiterate that no matter how many times your diagnosis changes, you’re still a part of this community, this Marfamily. And the way research is going, who knows? Maybe in another few years the powers that be will call what you have “Marfan” once again. It’s all part of the “fun” of having a rare disorder!

And again: The opinions offered at Musings of a Marfan Mom are for informational purposes only and are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified healthcare provider with any questions you may have regarding Marfan syndrome and any medical condition. Never disregard professional medical advice or delay in seeking care because of something you have read here.

Citation:
Loeys, Bart L., Dietz, Harry C., Braverman, Alan C., Callewaert, Bert L., Backer, Julie De, Devereux, Richard B., et. al. (2010). The revised Ghent nosology for the Marfan syndrome. Journal of Medical Genetics, 47:485-495.