Rubinstein-Taybi Syndrome

Medical

The Blue Book


The Blue Book is a compilation of articles from the 1998 International Family Conference that was held in Cincinnati, Ohio, July 10-13, 1998. It was edited by Jack H. Rubinstein, M.D., Nancy Lamphear, M.D. and Mark Shannon. It includes Anesthesia and Tethered Spinal Cord Information.

GROWTH CHARTS

Female Height Chart
Female Weight Chart

Male Height Chart
Male Weight Chart

 

 

Anesthesia

Anesthesia issues with Rubinstein-Taybi syndrome has always been a major concern for parents.

 

According to the medical literature, in some cases, individuals with Rubinstein-Taybi syndrome may have complications (e.g., respiratory distress and/or irregular heart beats [cardiac arrythmias]) associated with a certain muscle relaxant (succinlycholine) and certain anesthesia. Any situations requiring the administration of anesthesia or succinlycholine (e.g., surgical procedures) should be closely monitored by skilled professionals (anesthesiologists).

 

See also: Testing

             Book for Families

             RTS Pamphlet

RTS and Genes

This information was taken from the RTS Email List with Becky’s Permission.It has been corrected and modified slightly since it was posted.Becky and Stephen are the parents of Emma (born in January 1998) with RTS.

For more information please email Becky Celuzza personally at becky@celuzza.com

 

Hello to all.

My understanding of RTS (from the conference and a number of papers) is as follows:

When cells divide they must copy all of the genetic material in the nucleus, so that each daughter cell has a full complement. Our chromosomes are this genetic material. We (ideally) each have 46 chromosomes – 23 pairs. One copy of each pair of chromosomes comes from each parent. That is to say that in the beginning (fertilization) the egg has 23 chromosomes, and the sperm has 23 chromosomes. They are the only cells that have only 23 chromosomes. The fertilized egg then has 46 chromosomes. An amazing chain of events begins at fertilization. This single cell divides many times, and the right genes do the right things and eventually you get a baby.

Chromosomes are made of long chains nucleic acids (A, G, C, T are the abbreviations for the nucleic acids that are in DNA/chromosomes). These nucleic acids bond in pairs A to T and C to G. The structure of these nucleic acids is what gives DNA it’s double-helix shape. A particular sequence of nucleic acids defines a gene. There is a start sequence for each gene, then the gene itself, then a stop sequence. Thousands of genes exist on each chromosome.

To quote from “Biology” by Wessells and Hopson: “If a chromosome were the length of five letters on this page, the single slender DNA molecule it contains would stretch the length of a football field.” The double-helix of paired nucleic acids is tightly wound around proteins called histones. This chain of DNA wrapped around histones then coils about itself like a string being twisted. And as with a piece of string that continues to be twisted, it kinks upon itself to form super-coils. Suffice it to say that DNA is densely packed by the time it is in the form we usually see in pictures of chromosomes.

Many things can and do go wrong during the process of copying chromosomes during cell division. Sometimes a piece of one gene can be left out (a deletion), or a nucleic acid can be copied wrong (a point mutation where a G is replaced with a T, for example), or pieces of two chromosomes may swap places (a translocation), or sometimes an entire chromosome may be tripled (called trisomy) or even quadrupled (or more). Down Syndrome is also called Trisomy 21 because people with it have 3 copies of chromosome 21.

Most of the errors in transcription occur in places that don’t really matter – but it is these errors that have led to the diversity in our genes. Each mutation could be an advantage, disadvantage or neutral in nature. Advantageous and neutral mutations tend to stay around because the carriers live longer and therefore have the opportunity to reproduce more. (Of course this natural selection happens over many (thousands and millions) of years.)

In the case of RTS, it appears that a mutation occurs on one copy of chromosome 16, in a particular region that contains the CBP gene. (It would likely be fatal if the mutation occurred in both copies of the gene, because the protein is rather important.) The CBP gene codes for a particular protein that binds with another protein. Together this protein pair helps to activate a wide-range of other genes. There are other proteins that do similar, and sometimes overlapping, things. Because CBP helps to activate only SOME other genes, and there are other proteins that activate other genes, the mutation results in the broad array of symptoms that we see in all of our children with RTS.

The type of mutation varies from person to person. Dr. Hennekam indicated that they had discovered all varieties of mutation in their detailed FISH tests – translocations, point deletions, amino acid swaps.

Because most of the cells in our children have this mutation, they have 50-50 odds of passing it on to their children. Since they each have one good copy and one bad copy of chromosome 16, half of their eggs or sperm have a good copy.

In the case where members of the same family have RTS, but they are not directly related (as in parent and child, or grandparent and grandchild), it could be that there is a familial weakness in chromosome 16. That is, there is something about that family’s chromosome 16 that predisposes it to transcriptional errors. But I am just speculating here.

To summarize this rather long-winded explanation: RTS is genetic (as it is caused by a mutation on a chromosome) RTS is inheritable (as it can be passed from generation to generation) RTS is sporadic (as the mutation occurs randomly – although future research may discover some sort of non-random factor in the cause of the mutation)

I hope that this isn’t too confusing, and that it helped a least a little.

Becky Celuzza

Reference: Wessells, N.K. and J.L. Hopson. Biology. Random House. 1988. IBSN: 0-394-33732-8

 

3 Responses to Medical

  • I am the morher of Gustavo Pérez González , who has rts síndrome. The reason why i am writing id to know the problema using anestesia,because he id 17 trata old and last week it das detected a problem in his heart,and y want to know the risk that he has to be operate. Please debe me information un regard these matter. Beat regates, Laura González.

  • Laura,

    According to the medical literature, in some cases, individuals with Rubinstein-Taybi syndrome may have complications (e.g., respiratory distress and/or irregular heart beats [cardiac arrythmias]) associated with a certain muscle relaxant (succinlycholine) and certain anesthesia. Any situations requiring the administration of anesthesia or succinlycholine (e.g., surgical procedures) should be closely monitored by skilled professionals (anesthesiologists).

    Also this link has information from the conference in 1998 Conference.

    http://www.rubinstein-taybi.org/bluebook/anesthesia.html

    I hope that is helpful for you and Gustavo.

    Diane

  • Dear all,
    My daughter Sarah is now 9 months old. After she survived severe Sepsis with multi organ failure at the Age of 3 months and was diagnosed with several minor abnormalities (small PDA, vesicorenal Reflux, ..) and she didn’t achieve the regular milestones it was soon clear she was “different”. Already before the genetic testing I had done literature research and I was convinced she had RTS (I am a physician myself, cardiologist in Berlin). However it turns out she has translocation 10;16 with resulting partial trisomy 16 and partial monosomy 10. RTS genes are located on chromosome 16 – I think this can’t be a coincidence as she apparently shows many classic features of RTS. Does anyone know of similar cases? Is further testing/workup usefull or senseless?
    Anyhow, Sarah is still not crawling and not rolling over and only slowly learning to grasp for things but she is the most happy and uncomplicated babygirl know anywhere near!
    All the best,
    M.

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