DiGeorge Syndrome Demystifed

Does your face reveal what’s in your heart? It might – even more than you know. Take, for instance, a common group of birth defects – forms of a disorder called DiGeorge syndrome. Around one in 4000 is born with this syndrome, which arises from a deletion of a short segment of chromosome 22.  Among other problems, this deletion nearly always involves deformations in both the face and the heart.

Sculpture: Igor Mitoraj

The Institute’s Prof. Eldad Tzahor had already shown that face and heart go together: Very early on in the developing embryo,  the progenitor cells that will become heart and facial muscles start out together in the same “classroom” – a small area in the neck region. It’s not just incidental: It turns out that these cells not only arise from the same population, they need to “talk” to one another before they can move off to their respective places in the developing embryo.

But this didn’t explain why a single chromosomal deletion can cause a whole range of problems, from relatively mild defects to debilitating ones that require urgent intervention at birth. Tzahor and his student, Itamar Harel began looking for the answer in transcription factors -- the proteins that initially control genetic activity.

After identifying a number of relevant transcription factors, Tzahor, Harel and their collaborators around the world spent months developing and testing knockout mice that would reveal, in detail, the functions of these regulatory proteins in the development of the heart and face progenitors. Even more challenging was the creation of double-knock out embryos, missing two of the transcription factors.

Their ultimate finding was that the transcription factors form a network. There are upstream and downstream effects, but also sideways and indirect interactions. And that network tends to be at least partly self- correcting. When two transcriptions factors were lacking, the network’s outputs collapse, but with only one missing, others apparently stepped in to pick up some of the slack, resulting in a few “slip-ups,” but more or less complete hearts and facial muscles.

And yes, they revealed that, at least for those with DiGeorge syndrome, a face can tell something about the heart. They found that knockouts of specific transcription factors that were not previously linked to Digeorge were tied to distinctive combinations of facial muscle and cardiac defects resemble the congenital defects in babies. Tzahor and Harel suggest that certain birth defects in a newborn’s face could tell doctors to check for a corresponding heart problem.



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Greg, don't leave us in suspense ... what are the facial changes to look for???

By Amateur Observer (not verified) on 18 Jan 2013 #permalink

First of all, these were observed in mice -- more observations will be needed in humans to point to specific connections with any certainty. Second -- check out the paper if you have a subscription to PNAS.

ps -- the name's not Greg.

DiGeorge Syndrome is named after my father doctor Angelo DiGeorge who died three years ago. I enjoy following the tremendous research being done all over the world in connection with DiGeorge Syndrome, which is by all accounts the most common chromosomal genetic deletion syndrome. In fact, the actual incidence may be even higher than 1 in 4,000. I am also pleased that you correctly refer to it as "DiGeorge Syndrome" rather than as 22 q 11 deletion syndrome or by one of its many other monikers. For more than forty years it has been known is "DiGeorge Syndrome" in all of the medical text books and literature, but lately there seems to be a mighty effort by various institutions to rename it under there own flag. My father dedicated his entire career to this and to helping the children born with it. Accordingly, I urge all DiGeorge researchers, "DiGeorge families", and the entire medical community to respect and honor the remarkable man who first described the syndrome and who discovered the role of the thymus gland in human function by continuing to call it what it is, DiGeorge Syndrome.

By Christopher DiGeorge (not verified) on 18 Jan 2013 #permalink

Thanks for this.

Itamar Harel writes:

I agree that there is confusion in regard to the name of the syndrome. The reason for this is that the symptoms of DiGeorge syndrome vary considerably. The original classifications included velo-cardio-facial syndrome, Shprintzen syndrome, 22q11 deletion syndrome, Sedlackova syndrome and conotruncal anomaly face syndrome. All are now considered to be included within DiGeorge syndrome. The syndrome is usually caused by a deletion in the 22nd chromosome. However, some patients share similar symptoms without this deletion. As our research shows, a plausible explanation for this might be that additional 'genetic modifiers' of the syndrome could contribute to the syndorme.

Thank you for your comment.

So, any speculations on why the evolutionary need for facial and heart muscle connection?

Apparently, it goes back to some worm ancestors, who had no hearts. Digestion and circulation used the same muscles: check it out here.

facial features that I have unopened ear folds, long face, long bulbous tip nose, fish like mouth, small chin, hooded eyelids slanting downward. Christopher Di George I'm glad you and your father Dr. Anthony Di George agree with keeping the name all over facebook I've been fighting to keep it Di George Syndrome the doctors know we are susceptible to infection and calcium drops..THX

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Greetings! Very useful advice in this specific article! It's the small changes that will make the largest changes. Many thanks for sharing!

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By 手機行動電源 (not verified) on 25 Jun 2013 #permalink

MY daughter who was born in 1979 was diagnosed with DiGeorge Syndrome at Children's Hospital is Boston. How lucky were my wife and I that Angelo's son Tony was the admitting physician that evening. We subsequently moved to Philadelphia where Angelo saw Melissa at St Christophers. We were also lucky to live right wround the corner from their beautiful home on Queen Lane. Angelo, his wife, and Tony were always so gracious and supporting. Melissa passed in 2009 at the age of 29. she lived at home and lived a very productive life (google her name). We owe it all to Tony and his dad. Tony continues to practice, and used to have a website, which I have been unable to locate of recent. If anyone has it please forward

By Bob Doyle (not verified) on 22 Sep 2013 #permalink

This was such an interesting read, thanks for sharing this! It is so fascinating to know that the progenitor cells of the heart and facial muscles communicate with one another before moving to their separate regions of development in the embryo. Also, the fact that the network of transcription factors can partially self-correct itself is phenomenal. How amazing is the human body!

By epstead 15029574 (not verified) on 15 Apr 2015 #permalink