In August 2011, we welcomed our third child into our family. After an uneventful pregnancy, I delivered Peyton Grace via scheduled C-section and we brought her home four days later. It became apparent pretty early on that Peyton was not developing similarly to our other children. She had an extremely difficult time sleeping and could not be soothed unless she was tightly bundled or in a swing on the highest speed setting. She also had trouble keeping her feedings down and other concerning digestive issues. She later would fail to meet all of her milestones. On her first birthday, Peyton could not sit without support for more than a few seconds and was not babbling. We called in Early Intervention and began every type of therapy imaginable. Progress came painfully slow.

When she did make progress, it was followed by months of no new development. At this time we also began genetic testing and other medical testing under the advisement of our pediatric neurologist. Peyton developed difficult to control seizures that would later result in her being put on the ketogenic diet. After a few years without results, we decided to have the Whole Exome Sequencing (WES) run. Eight months later, we received a non-result. Peyton had a variant on her DDX3X gene line, but it was not yet known if this gene was the cause of her struggles or not. Science had not caught up with the technology. We did know that this was a de novo finding, meaning that it was not inherited from either parent. After the results came in, we continued on with life, doing everything possible to help Peyton be her best self.
In May 2015 we received a surpising phone call from our Genetic Counselor. Other girls had some of the same struggles as Peyton and their WES testing was also turning up findings on their DDX3X gene line. A paper was soon to be published in The American Journal of Human Genetics (Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling-August 2015) and a clinic in Pennsylvania was planning a DDX3X family day to go over the findings. The Clinic for Special Children, located in Lancaster, Pennsylvania, put on an amazing day with a variety of specialists. The Genetics Counselor, Karlla W. Briggati, welcomed us with open arms and patiently answered our questions. Eight families, including mine, were fortunate enough to attend the day. We learned that approximately 50 girls in the world are currently affected by a variant on their DDX3X gene line.

Credit to Dan Marschka -Staff Photographer LancasterOnline.Com

Credit to Dan Marschka -Staff Photographer LancasterOnline.Com

This number is expected to grow as WES becomes more readily available. Like beautiful snowflakes, each of our girls is remarkably similar, yet exceptionally unique. This specific condition is not inherited and affects only girls. (Boys can inherite a variant on their DDX3X gene line from their unaffected mother)
*100% of the girls have Intelictual Disability in varying severity as well as having limited to no speech
*32% have low weight
*76% have hypotonia
*16% have epilepsy
*45% have movement disorders with some being unable to walk
*53% have behavior issues
A list of other symptoms includes, but is not limited to: abnormal findings in brain MRI, skin abnormalities, hyperlaxity, visual problems, hearing loss, cleft lip or palate, precocious puberty, and scoliosis.
In addition to the amazing knowledge that I gained while visiting The Clinic for Special Children, I found a support system of people who understand exactly what we are going through. A DDX3X mom from South Dakota started a Facebook page for our girls. We now can log on and talk to other families and rally support for one another from near and far. Families from the United States, Cananda, Ireland, the U.K. and the Netherlands are lending a caring ear and offering up suggestions on therapies, procedures, medical equipment, and more. As this group continues to grow, so does our understanding of how complex DDX3X is.
This is just the beginning of our story with DDX3X, but we have so much hope for the future and now know that our daughter is not alone in her journey. Until all of our daughters can share their own stories, we will be the voices for our DDX3X girls!

12 thoughts on “DDX3X: When Whole Exome Sequencing Reveals a Gene Variant that Science Hasn’t Caught Up To”

  1. Jon Soini says:

    Hi there! Our daughter Sparrow, born in 2012, was just diagnosed w/ this syndrome for the DDX3X gene line, if anyone’s reading this, can you reach out to jon at soini dot com.

    We’d love to get in touch with similar families and share our daughter’s journey and symptoms (many which align with the ones in this article).

  2. Natalie Chapman says:

    Hello.
    So glad this is finally happening!
    My name is Natalie, I live in Cornwall, England. My daughter Hollie had just been diagnosed with the DDX3X fault. She will be 9 in march. email me I would love to hear from you. We have 3 daughters age 12 8 and 5 Hollie is in the middle. Natalie.

  3. Sophie valentine says:

    Hello my daughter lily was diagnosed this year with ddx3x syndrome we live in London England. Lily is 8 years old.we Would love to hear from other parents. I was so happy to read this just to hear that there are other family’s who understand.

  4. Mars clare mccluskey says:

    Hello my daughter was diagnosed in march 2015 with ddx3x syndrome she will be 12 in June she is very complex and I would love to hear of other parents about this condition .

  5. Beverly Schumer says:

    Our daughter Abigail was diagnosed today, May 3, 2016, with ddx3x related disorder. She is 17 and some conditions were present at birth and other appeared as she developed. I am interested in sharing our experiences with other parents. Is there an established site for this type of communication? We live in Michigan.

  6. Elizabeth Maly says:

    Hi. I am so glad to hear from you. This story is about my daughter. Are you on Facebook? We have a wonderful group

  7. Elizabeth Maly says:

    Hi. I am so glad to hear from you. This story is about my daughter. Are you on Facebook? We have a wonderful group

  8. Elizabeth Maly says:

    Please feel free to email me elizabethahmaly@gmail.com

  9. Elizabeth Maly says:

    Please feel free to email me elizabethahmaly@gmail.com

  10. Celia says:

    Hello,
    Last week Our daughter Paula was diagnosed by ddx3x syndrome She is 18 years old. From birth She had a lot of development problems, And unfortunatly she is not able to talk/ speak. We live in the Netherlands, so my english might be sometimes written wrong.. Sorry for that. I would like to join Facebook page.. Can you tel me there are parents from the Netherland om thuis page.? Thank you

  11. Elizabeth Maly says:

    Hello,
    Definitely join the ddx3x Facebook page. There are other families from the Netherlands on the page. I think that you will find it very helpful

  12. Esther says:

    My name is Esther …i am from Spain…today we have receive the inform of our genetist…Our daughter Valeria has DDX3X…could someone help us?? Thank you very much…

Comments are closed.