What’s in Your LDS Family Tree? Genetics, Variability, Outcomes (September 1, 2020)
34:01-37:57
Should relatives who show characteristics of Loeys-Dietz syndrome including aortic dilation yet don't test positive for the family's identified LDS gene continue to explore LDS as an expected cause?
MacCarrick:
大動脈拡張などのLDSの特徴がありますが、家族と同じLDS原因遺伝子を対象とした遺伝子検査の結果が陰性です。この場合でもLDSと考えて経過観察すべきでしょうか？というご質問です。
So, that's actually not an uncommon situation. On a regular basis we find what we truly believe to be the gene and the change that's causing a condition like Loeys-Dietz syndrome in a family but recognize that there are outlier individuals in that family typically one, sometimes more than one, who show some degree of aortic enlargement but come back negative for the familial gene change. That doesn't mean that, that person has Loeys-Dietz syndrome but does suggest that they have some other genetic predisposition for their aorta to be bigger than it should be. You know, if they have all the other outward features of Loeys-Dietz syndrome, skeletal and craniofacial features that really suggest that they have Loeys-Dietz syndrome. Probably they should get in touch with the lab that did the testing to make sure there wasn't a sample mix up because those kinds of things although rare can happen but if that's not the case they need to continue to be followed by a cardiologist if their aorta gets to a worrisome size. They should consider using medications and perhaps the need for surgery.
Dietz:
このような状況は珍しいことではなく、日常的に起こりうることです。我々は家系内でLDSに似た病態を引き起こしているのは、LDSの原因遺伝子に変異が生じているからに違いないと考えます。ところが実際は、程度問わず大動脈拡張がみられ、家系内の他の方に見つかっている原因遺伝子の検査結果が陰性となる患者さんが、家系内に通常一人あるいは時には複数いらっしゃることがあります。このような患者さんはLDSというわけではなく、それ以外の他の遺伝的な素因によって大動脈が拡張していることが予測されます。骨格系や頭蓋顔面的特徴といったLDSの外見的特徴が全て現れている場合にはLDSと思われますが、念のため、検査を行った施設に連絡を入れ、採取した検体の取り違えがなかったかどうかを確認してください。こうした取り違えは稀ではありますが、起こる可能性はあります。そうした可能性が除外された後は、大動脈が危険なサイズまで拡張していないか、循環器内科での経過観察を継続する必要がありますし、薬の服用や外科手術なども検討しなければなりません。
You know, I can tell you that in over the years that I've been doing this there are probably a dozen families or so where I feel confident that there are two different gene changes causing aortic enlargement in that family and there's at least one family where I feel very confident that there are three different genes causing aortic enlargement in that family, so it's fortunately rare but it does happen.
Dietz:
長年にわたる診察の中で、家系内の大動脈拡張の原因が、2つの異なる遺伝子における変異だと確信できる症例もありましたし、3つの異なる遺伝子における変異が原因だったと断言できるような症例も少なくとも一件ありました。ご質問のケースは珍しいことではありますが、起こる可能性はあります。
And I think this was a variation of a question that was a little bit later on is that I think we get a similar question in terms of someone who tests negative, who has a normal aorta but who has some like mild hypermobility or mild scoliosis but they have a normal aorta and in those cases I don't necessarily know that it's necessary to be aggressive in further testing unless they have aortic dilation in a family member.
MacCarrick:
この質問は後ほどご紹介する質問と同じ系統の質問だと思います。遺伝子検査が陰性で、大動脈の太さも正常だが、軽度の関節の過可動性や軽度の側弯症がみられるといった質問内容ですが、家系内で大動脈の拡張がみられる場合は別として、そうでない場合には、積極的に遺伝子検査をする必要があるとは思いません。
Yes, as Gretchen mentioned connective tissue findings are really pretty common in the general population. If you look at families with Marfan syndrome or Loeys-Dietz syndrome it's not at all uncommon to find occasional family members that have loose joints or a little bit of indentation of the chest wall or perhaps very mild curvature of the spine.
Dietz:
Gretchenのいうとおり、結合組織疾患に関連する所見は、一般集団においても非常に多くみられます。Marfan症候群やLDSの家系をみると、関節が緩かったり、多少の漏斗胸だったり、非常に軽度の側弯がみられても全く不思議ではありません。
What is uncommon is to find people in those families who have many of those findings in combination so that should really be the red flag. If someone is showing up with scoliosis and pectus deformity and severe nearsightedness at a young age and skin stretch marks somebody needs to take a real careful look at that individual. As Grenchan mentioned if somebody just has one finding that's really common in the general population. You know, as long as the testing has been done that excludes that, that person carries the familial gene variant I think that they can be largely reassured.
Dietz:
ですが、これらの所見が複数組み合わさって現れるケースは赤信号です。側弯、胸骨変形、強度近視、ストレッチマークが現れているお子さんの場合には、非常に注意深く経過をみていく必要があります。Gretchenからもあったように、一つくらいの特徴は一般集団でも普通にみられます。遺伝子検査の結果、家系に共通する原因遺伝子の変異がみられなかったのであれば、安心してよいと考えます。
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。
