Congenital Anomalies Research & Exploration (CARE) Study

1. 1. Sign up by emailing ChungGeneticResearch@childrens.harvard.edu. Please include "LC Voices Research" in the subject line.

   2. Within one week, you should receive electronic consent forms by email.

   3. Sign and submit consent forms for all participating family members.

   4. After consent is completed, you will receive a link to complete the study surveys.

   5. Complete and submit all surveys.

   6. Once surveys are submitted, saliva collection kits will be mailed to you, usually within two weeks.

   7. All participating family members* will need to complete saliva collection and return their samples by mail.

   8. After the laboratory receives saliva samples from all family participants, results are typically available within 3–6 months. If a sample is not collected properly, it may not be usable and a new sample will be needed, which can extend the timeline.

   9. If a genetic change is identified, you will be contacted by email and by phone to review the results in detail.

   10. If no genetic findings are identified at this time, you will receive an email notification. Samples may be reanalyzed over time as genetic knowledge advances, and you will be contacted if new findings are identified in the future.
       
       

*NOTE: Saliva samples from each family will not be analyzed until adequate samples are received from all participants in that family.

Sponge Collection Option

If your child is 3 years old or younger, a sponge for saliva collection will automatically be included in the sample collection kit. If your child is older than 3 years and unable to spit into a tube, email the study team and request a sponge for saliva collection. Then follow directions (starting at a1:15) on this video.

Boston Children’s Hospital

Contact: Study Coordinator Alexa Geltzeiler

Email: ChungGeneticResearch@childrens.harvard.edu
Phone: 617-919-0605

Cincinnati Children’s Hospital Medical Center

Contact: Study Coordinator Pranjal Patel

Email: pranjal.patel@cchmc.org

Phone: 513-636-3929

By Dr. Wendy Chung, MD
Chief of Pediatrics, Boston Children’s Hospital

You may have asked yourself the following questions: Why was my child born with a laryngeal cleft? What caused this? What will the future hold?

To a certain extent, every child is different and the answer to these questions may be different for each child with a laryngeal cleft. Your doctors may have been able to provide some answers, but perhaps not all the answers. Because we are doctors taking care of patients with a laryngeal cleft and other related conditions, we want to find answers to your questions and need to perform research to learn about what we don’t yet know.

One possible explanation is related to genetics. Genetics may not have all the answers for all individuals with a laryngeal cleft, but it likely will provide some information for some people. It’s for this reason that we are starting the genetic study of laryngeal clefts in collaboration with Laryngeal Cleft Information. 

How often do you expect to find a genetic cause of laryngeal cleft?

I actually don't know the answer to that very simple question. That's why we're doing the research. If I had to guess, I wouldn't be surprised if it’s 10% initially. I think that's going to be the minimum and I think we're going to go up from there. It may be that as we go on it becomes 20%, and then goes up to 30%.

The more people that we have doing this together, the higher that number goes up, because we start seeing connections between individuals, between families. We start seeing the same gene that's involved not just in one family from Iowa, but we see another family from Missouri, another family from Wisconsin, another family from Texas.

How many genes could be involved?

I don't expect there to be just one gene for laryngeal clefts. I actually expect that there are going to be probably dozens of genes, and each gene may have different answers to these same questions. So that is different information about prognosis or what to expect, different information about implications for family members. We hope that we can provide not just one answer, but actually answers that are tailored for each of you. 

What happens if you find a cause in my/my child’s genes?

If we do find what we think is the genetic cause of the laryngeal cleft in your family, we're going to give you a call and email to talk to you about what that means. And you'll get a clinical test report so that you and your doctor can use that information for your clinical care. You shouldn't need your doctor to order an additional genetic test. If you get a positive result, you'll get a clinical report that says that.

What happens if you don’t find a cause in my/my child’s genes?

If we don't find the answer, we are going to keep looking. We're not going to give up. As more and more families join the study, we're going to keep reanalyzing that data. We expect we'll do it probably once a year. So even if you don't hear a positive result from us right away in that first three to six months, we'll continue looking. As long as we know where to find you, even if it's two, three years from now, we'll continue to reach out when we have that information.

If I have a child with a laryngeal cleft, what is the likelihood of having another child with it?

That is dependent on your family history and your own personal circumstances. If you have a family history where there's more than one person with a laryngeal cleft, we need to handle that on a one-by-one basis, but that risk could be as high as 50%. We know that based on looking at some other congenital anomalies for individuals, where there's no family history, the chance of it happening again is likely much lower, but likely not zero. Probably less than 10%, maybe even less than 1%, but I don't know until we do some more of this research to get the answer to that question.

The CARE Study has enrolled about 50 laryngeal cleft families since the beginning of 2025. Of those 50 families, 12 have completed the testing, and researchers have analyzed their samples and sent back the results. The study team is receiving one to two new enrollments every few weeks.

In the small numbers of families analyzed, no new genetic causes have been identified. However, it's important to understand that if no genetic cause for a family is found, it doesn’t mean there isn’t one. There could still be a genetic cause that researchers do not yet recognize, but will in the future as more families are analyzed and as patterns across families emerge.

The genetic causes of laryngeal clefts are not well understood currently, so the study is focused on trying to identify genes that may be related. As time goes on – and more and more families join the study – researchers will have a better chance of identifying genetic changes that may be causing this birth defect.

After the initial sequencing, family samples will be retested about once a year. If a genetic cause is identified in your family in the future, you will be contacted by the study team, who will discuss the result and send a clinical report at that time.

Saliva Kits

Don’t forget to send back your samples! About 25% of LCN families have not yet sent their samples back for testing.

Collection Issues

Proper saliva collection is key to ensuring researchers can actually test the sample. For a variety of reasons, some of the samples are not adequate, and families are being asked to resubmit a sample, which delays results. 

Collection Tips

• No eating or drinking anything for at least 30 minutes before collection.

• Consider leaving the kit by your bed and collecting saliva first thing in the morning.

• Fill the tube up to the line with saliva – not bubbles.

• Carefully read the included directions.