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

[ShellyMoore]

I'm going to go out on a limb here, but here goes...

Do we know if there could be 1 or more defective gene sub-component like a particular protein or RNA that could be present in most, if not all, of the chromosomes that be responsible for CDH showing up in so many different chromosomal locations?

Is it possible that CDH could wind up being another connective tissue disorder? After all defects in connective tissues can do some strange things... Maybe it could account for some the variations like eventrations & Late Presentation CDH (LP-CDH)???

*** Full Disclosure: Our CDH family is one of a 1/2 dozen families with Marfan syndrome, and there are several on the list with Ehlers–Danlos & Beals. ***

Shelly Moore

[JuliaWynnMS]

There are several different regions on chromosome 17 where we have seen extra or missing pieces in children with CDH. We are not yet sure what specific genes on chromosome 17 are the critical regions for CDH.

Our study is open to those who have a known chromosome deletion or duplication as well as those who have an unknown cause. Both types of cases are very informative to our study and will ultimately help us to better understand all of the different genetic causes of CDH.

[JuliaWynnMS]

Shelly,

You are not going out on a limb you are thinking like a scientist! We do think that while there are a lot of genes that are involved in the development of the CDH many of these genes are related - they interact with each other in development. For example there are two gene in the GATA family that have been identified to cause CDH. While they are two different genes, the proteins they make interact with each other and are both important in the development of the diaphragm.

With regards to your question about a connective tissue disorder. Yes I do think that a small proportion of individuals with a CDH have one because of a connective tissue disorder (your family and the others you listed might be examples). This is just one example of how diverse the genetic causes of CDH are.

All the best to your family!

[JuliaWynnMS]

Tracy,

Congratulations on your little boy.

You have a very thoughtful question about CDH and genetic causes.

There are several different ways that we think a genetic mutation occurs or is inherited to cause a CDH

1) A genetic mutation is not inherited from the mother or the father but rather happens new in the child at the time of conception when the egg and sperm come together. We know the new genetic changes occur in every pregnancy and we think that in children who are born with birth defects these new genetic changes disrupt important genes. These genetic changes happen by chance and there is nothing a parent does or doesn't do to cause them.

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.

3) 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.


You asked about your child's risk to have a child with CDH. My hope is that we will have a much better understanding of the genetic causes of CDH by the time your child is having children because of families like yours that participate in genetic studies. The risk of an individual with a CDH having a child with a CDH (recurrence risk) is dependent on the specific genetic cause of their CDH. This risk can range from <1% to as great as 50%. I encourage everyone to see a geneticist or a genetic counselor prior to starting a family so that they can help to determine the recurrence risk based on that individuals family and medical history and possibly help them to pursue reproductive options to prevent their children from having a CDH if they wish to do this.

[JuliaWynnMS]

Casey,

Thank you for your question. I'm sorry to hear about your husband and hope he is well now.

For the most part we think that genetic risk for conditions is independent. We don't think having a child with CDH does not increase your risk for other genetic conditions that are not related to the CDH.

Best

[JuliaWynnMS]

Casey,


I'm sorry to hear about your husband I hope he is doing well. We think that genetic risk is independent. We do not think that having a child with a CDH increases a person risk for other genetic conditions that are NOT related to the CDH.

SORRY. I thought my previous reply didn't show up.

[AmandaPlakholm]

Julia,

We never really talked to our doctors that much about the reason why this happened. We met the genetesist and 2 hrs later had an amnio because she said there is sometimes CDH'ers who are stillborn or live only a month because of trisomy --. I can't remember the number but I'm wondering do you know how often that occurs? Also would the amnio have told them if there was a reason for her CDH? We always just assumed there was no chromosomal issues with our daughter because of the amnio.

[JuliaWynnMS]

Lizz,

Thank you for your interesting question. Typically the things that cause a CDH in a neonate are different than the things that cause a CDH in an adult. Sometimes adults can have a CDH if they had an accident or a surgery where their diaphragm was damaged. There is also a condition called a hiatal hernia where the stomach herniates through the hole in the diaphragm where the esophagus passes through. If neither of these situations describes your grandfather it is possible that his CDH is related to your CDH.

If all of your daughters are doing well, there is likely little screening that can be done at this time. You should always be careful to inform their doctors of the family history of the CDH.

Best

[JessAlbin]

Hi Julia, my daughter is a rCDHer that is now 6 weeks old. I'm wondering if you have discovered any information regarding why right-sided cdh's happens instead of left and why its more rare. Also, it seems there's a much higher rate of unpredictability regarding right-siders and how they will react after being born and to surgery. Has there been any information discovered regarding why that happens? Basically I'd love to know anything being discovered about rcdh because I know there is currently very little information available. Thank you for all you do! We just recently began participating in the study and I hope it helps!

[JuliaGrafe]

Julia,

I was born eighteen years ago with CDH on my left side. I am curious on whether or not it is hereditary. No one else in my family has CDH, but I am still curious on whether I could pass it on to my future children. Also, because of my birth genetics is my passion. Is there any advice on college majors/masters that will help me become a genetic counselor? I plan on finding out why CDH happens and how it can be prevented. Thank you.