米国マルファン症候群患者団体The Marfan Foundationからの情報を中心に、マルファン症候群や関連疾患についての海外情報を翻訳して発信します。


What’s in Your LDS Family Tree? Genetics, Variability, Outcomes (September 1, 2020)




So last question because we're running up on time and this is actually a question I've been struggling with as well. Knowing that testing panels are changing, your thoughts on if someone has had a negative panel but now that SMAD2 is being offered, like, should we be offering just that as a single gene? Like, what are your thoughts on pursuing that? Now that it hasn't been on panels and can you talk a little bit about Loeys-Dietz type six potentially?




Yeah, so people should take a careful look at you and say, you know, "What there is?" "This new gene available on a panel?" "Does that gene make any sense for you as an individual?" you know, "Does it match with your features?" "Is it plausible that your condition would be caused by a change in that gene?"




The answer is yes, then it may make sense to do that testing and to be honest I would choose the method that's most reliable and least expensive, you know, if you can get if it's only that one new gene that's available on the panel and it costs less to get that one gene sequence than to repeat the whole panel. I would choose to just get that one gene sequence. 




If, however, since the last time that you were tested there are five new genes on the panel and three of them could make sense for you it probably would make sense to get the panel repeated rather than to have each of those three other individual genes done.




So Loeys-Dietz syndrome type 6 or whatever someone is referring to it as caused by mutations in SMAD2, can have skeletal and craniofacial features that overlap with Loeys-Dietz syndrome. It can have aortic aneurysm although there are people, there are quite a few people that have inherited the familial SMAD2 mutation that for reasons we don't understand, are not showing aneurysms early or even late in life. It's not uncommon to see people with a SMAD mutation that never got the aneurysm that was seen in their brother or sister or aunt or uncle that led to the initial testing. 




What also is not seen in people with SMAD2 mutations to the same extent as TGFBR1 or 2 or SMAD3 mutations is aneurysms elsewhere throughout the circulation or aneurysms that are tearing at small dimensions, you know, so that's, you know, that's what's making people, you know, giving them incentive to collect more information before deciding what proper management principles are, for example, in people with, with SMAD2 mutations. 




Certainly in some of the cases when you see the an individual with a SMAD2 mutation there's little doubt in your mind that it's in the Loeys-Dietz syndrome spectrum of disease. If you just look at their face and look at their skeleton and even look at their aortic root but then there are these other factors that suggest that this is at a new mild end of the spectrum, milder than what we've seen before in other forms of Loeys-Dietz syndrome. 




You know, we have to consider that the clinical spectrum of severity in aortic aneurysm conditions is very broad in all the conditions we think about. You know, we see young children with Marfan syndrome, who at birth have really striking skeletal and facial features, have very severe and rapidly progressive aortic enlargement and valve dysfunction within the first few months of life, who may require surgery within the first two or three months of life to try to save their lives and then there are other people with Marfan syndrome. No one would argue that they don't have Marfan syndrome, who you would not pick out of the crowd at age 75, who perhaps have some very mild scoliosis and some nearsightedness and an aortic root at age 75 of 4.0 centimeters.




So, you know, the the issue of wide variation in clinical severity is not new to us and, you know, I think that there are good practices and rules in place to make sure at every possibility that you're not making recommendations based upon the average person with that condition but rather are making recommendations based on everything that you can learn from that person sitting in front of you so that's what you should be challenging your doctors to do. 



The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.

The Marfan Foundation は、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.org にアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。