CHERUBS Medical Expert Series: CDH & Genetics (Nov 4-11, 2013)

[NeilRubenstein]

Julia,

I am wondering if there are any new findings on the increased chances of having another CDH child. I know that the generally accepted probability goes up to 2% after your first child with CDH. But what about after you have 2 children with CDH. Does the probability increase even further with your 3rd child.

Thank you very much

Neil

[Courtney Deuro]

Dear Julia,
Thank you for answer these questions! How does an older survivor get involved in these studies? I'm 23 and want to help learn more. The genetic aspect fascinates me because I'm still debating on having a child of my own. I've been told that my amniocentesis was "spot on" for no abnormalities. Has amniocentesis changed in anyway in the past 23 years? Are there more genes that get look at? (Ex: 23 years ago they looked at 300 gens but now they look at 500.)

Do you know any new information about the link to diaphragm and lung development (other than organs being in the way)? About ten years ago I was in Pittsburgh for consultation about a potential back surgery and while we were there we had the opportunity to talk to a surgeon with CDH experience. He talked about experiments they were doing with cats by inducing controlled CDH to see if its the diaphragm that stops forming first which causes the lung to stop, or vise versa. I haven't heard anything else since - I was turned down for the surgery and never visited that doctors again. I doubt my parents would remember his name.

Thank you again!
- Courtney

[AmandaS]

Neil,
I am pregnant with my third child, my other two children have CDH (one right, one left). We met with a genetic counselor at Minneapolis Children's Hospital, and were told we have between a 10-25% chance of having another baby born with CDH. If our children underwent genetic testing, depending on the results, the chance could increase our decrease.

I know you posted this to Julia, but I thought I'd add my info. Hope that's ok.

Also, I've been following Brody's journey on Facebook, I'm so glad he's doing well! What a fighter, and what a handsome little man!

Amanda

[NeilRubenstein]

Thanks, Amanda. Interesting information....curious what Julia's response will be. And thanks regarding Brody...we'll keep him.

[BRoper]

Hi Julia,

Our daughter passed away 4 months ago from CDH along with several VSD's and an interrupted aortic arch. We were pregnant with twins and lost one twin very early on. We are also part of your study and have several questions. First of all if you do find any genetic cause during the study how long does it usually take to get the results? Is CDH more common in twins? I know the risk of having another child with CDH is about 2% but does the risk increase if there was a heart defect as well? Thank you for taking the time to answer our questions. And thank you for trying to find a cause to this devastating birth defect.

Brooke

[BRoper]

I have one more question I forgot to include. I read where you think it can be caused by a connective tissue disorder. I was diagnosed with a connective tissue disorder after I gave birth to my oldest daughter. If it is a connective tissue disorder are you able to determine that through the study and does that mean it was inherited from me?

Thanks again,
Brooke

[JuliaWynnMS]

Amanda,

I hope your daughter is doing well now. The amniocentesis you had during your pregnancy with Liz would have detected large genetic mistakes in the chromosomes - having an entire extra or missing chromosome- but there are smaller genetic mistakes that we are now able to detect that would not have been detected on the chromosome analysis. You can have you daughter evaluated by a geneticists who can explain the more expanded testing available. Approximately 15-20% of children with a CDH have a genetic cause that can be detected by available testing. Most of these children have second birth defect. We think that many other children have a genetic cause but it is too small to be detected by current available analysis. We are looking for these smaller genetic changes in our research study. I can discuss this more with you by phone if you are interested. 212 305 6987 or if you would like me to help you find a geneticist in your area.
Best,
Julia

[JuliaWynnMS]

Neil,

We cannot know the exact recurrence risk until we understand the specific genetic cause in your family. I have listed the two possible ways the CDH could have been inherited in your family. In scenario 1 the chance of it to happen again with each pregnancy is 1 in 4 (25%). In scenario 2 the chance of it happening again is less certain because the mutation does not always cause a CDH when it is inherited. In these cases we would say the chance may be as high at 50% because with each pregnancy there is a 1 in 2 chance (50%) to pass on the mutation but the child may not develop the CDH. If we know the exact molecular cause of the CDH in the family, there are reproductive options that family can pursue to prevent the CDH from happening again if they wish.


1) A child inherits a genetic change from the mother AND the father. This genetic change alone in the mother or the father does not cause a CDH but when the child has BOTH genetic changes this causes a CDH. We think this type of inheritance is most likely when a family has more than one child affected.

2) A child inherits a genetic change from the mother OR the father and this causes the child to have a CDH. The parent with the genetic change may have a very mild CDH and never know that they have it or they may have other protective genes that cause them not to have a CDH even though they have a genetic risk. We think this type of inheritance is much less common than the first type. We think of this type of inheritance when a family has a child affected with a CDH and a parent is affected or a more distant relative like a aunt, uncle or cousin is affected.

[JuliaWynnMS]

Brooke,

Thank you for your patience with the study. I know that so many people have participated in the study buy they have not yet received test results. We are working very hard on all of the samples to try to identify the genetic cause of the CDH. We have learned that the genetic causes of CDH are very complex and not always easy to identify. We know of over 100 different genetic causes!

We contact all families if and when we identify a genetic cause but we are not able to contact families each time we complete a genetic test on a sample. I encourage everyone to contact me by email jw2500@columbia.edu or by phone 212 305 6987 to ask specific questions about their family. I can tell you what analyses have been done and what this means about the risk that the CDH is genetic in the family.

I sent you a private email in response to the connective tissue disorder question. There are many different types of connective tissue disorders and only a few have been associated with CDH.

Best,
Julia

[JuliaWynnMS]

Courtney,

Thank you for your interest in our study. We enrolled individuals of all ages with a CDH.
The testing that can be done on an amniocentesis has changed quiet a bit in 23 years and I would encourage you to speak with a genetic counselor as you prepare to start a family of your own. I can refer you to someone close to you if you like.

There is still a lot of work on going with lung develop. Many of the studies are focused on trying to understand it so we then know how to treat it. Other studies are looking at trying to improve the lung development inutero while the fetus is growing. Presently there are no on going human studies of medications to improve lung growth in individuals with CDH but our hope is that through research studies and generous families we will better understand CDH and lung develop which will allow us to develop better treatment.

Please contact me by phone or email jw2500@columbia.edu or 212 305 6987 if you would like to discuss participating in the study.

Best,
Julia