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In the past 25 years the frequency of babies born with Down’s syndrome has doubled, according to this report in The Manichi Daily News.

It could be a translation issue, but the use of the word ‘frequency’ suggests this isn’t just a matter of the number of cases of Down’s syndrome increasing in line with (or below the rate of) increases in birth rates in general.

The Manichi news report mentions this statistic in relation to a planned epidemiologic study to probe the connection between the environmental use of chemical substances and childhood illness.

It does not state whether the research will investigate the impact of the environment on the cause of Down’s syndrome, which would be interesting, or just look at the impact of the environment on children with Down’s syndrome.

The reports states:

“The ministry’s study will investigate the amount of chemical substances that enter children’s bodies and investigate the relationship with abnormalities in their immune systems, development disorders and other conditions. Assistance will be sought from about 60,000 pregnant women across the country from fiscal 2010. In addition to collecting umbilical blood, researchers will conduct regular examinations of children from around the time of their birth until they reach the age of 12 to determine their health status. The results of the survey are expected to be compiled in about 2025.”

I’ve been meaning to write a quick post on the genetics of Down’s syndrome for some time, but I haven’t got round to it. I wanted to write about as a record for any visitors looking for info about genetics, but also in the hope that it will help me understand/remember it. Thinking about G’s karyotype results has spurred me on, so I’m going to bash this out as quick as I can.

There are three types of Down’s syndrome:

But first, the basics:

The human body is a collection of cells. Each cell contains a collection of genes. Genes are made of of DNA. Chromosomes are groups of genes. There are 46 chromosome in 23 pairs in all cells (apart from the sperm and egg cells, which have 23 chromosomes each). One pair comes from the mother, the other from the father. Each chromosome has two sections, known as the ‘long arm’ and the ’short arm’ (this bit is relevant to translocation). The body grows by creating new cells. In order to do this a copy of the chromosomes in each cell is produced, before the cell splits in two with a set of chromosomes in each of the new cells. This is called mitosis. Egg and sperm cells divide using a different process called meiosis, but we don’t need to bother with that now.

Regular Trisomy 21
About 94% of people with Down’s syndrome have trisomy 21, which means they have an extra chromosome (No 21) in every cell, making 47 chromosomes per cell in all. This occurs due to unusual cell division, the cause of which is unknown. The extra chromosome comes from an egg cell or sperm cell which is produced with 24 chromosomes rather than the usual 23.

Karyotype for regular trisomy 21

Source: Wikimedia commons/Human Genome project.

Why does this happen?

No one knows. It is not hereditary – the production of the abnormal egg or sperm cell just happens. Mothers over the age of 35 are more likely to have a baby with Down’s syndrome. One theory for this is that all women have eggs with 24 chromosomes but the body uses the normal egg cells first. Another theory is that the older a woman is, the harder her body works to ensure that the baby is not miscarried. There is some debate over whether the age of the father has an impact, given that men produce new sperm throughout their lives, whereas women start making their egg cells while they themselves are still in utero, however recent research indicates that the age of the father is significant.

Translocation
About 4% of people with Down’s syndrome have translocation, which means that they have an extra part of chromosome 21 attached to another chromosome (either 13, 14, 15, or 22). Translocation occurs when the small arms (see basics above) of chromosome 21 and another chromosome break off and the two long arms join together. There is an extra copy of a large part of chromosome 21 so the effect of translocation Down’s syndrome is no different from trisomy 21.

Why does this happen?

In two-thirds of cases this translocation occurs during the formation of the egg or sperm cell. No one knows why. When the egg or sperm cell fuses with a regular sperm or egg cell one of the created 46 chromsomes will have an extra bit of chromosome 21 attached to it, which acts as a single chromosome in cell division, and all cells therefore have an extra chromosome 21.

In one-third of cases the translocation is inherited from one of the parents who has two number 21 chromosomes in each cell, one of which is attached to another chromosome. The parent does not have any traces of Down’s syndrome as they have the correct amount of genetic material (balanced translocation), however it is possible for their egg or sperm cells to pass on both the translocated chromosome 21 material and the free chromosome 21, resulting in their baby having Down’s syndrome.

The age of the parents is not a factor in translocation.

Mosaic
About 2% of people with Down’s syndrome have mosaicism, which means they have an extra chromosome 21 in only some of their cells. Depending on how many cells are trisomic, and which ones, a person with mosaic Down’s syndrome may be less affected physically and mentally than those with regular trisomy 21 and translocation.

Why does this happen?

No one knows. Mosaicism occurs after conception. As the cells divide and multiply in one cell with 46 chromosomes the pair of 21 chromosomes fails to separate (nondisjunction). This cell divides into one cell with 47 chromosomes (and an extra copy of chromosome 21) and one with 45 chromosomes (which does not survive). The cell with 47 chromosomes survives and continues to divide , producing further trisomic cells alongside the other ordinary cells. The age of the parents is not a factor in mosaicism.

(For more on mosaic Down’s syndrome see this post)

Like I say, this is not meant to be authoritative, and I’m sure I’ve missed out a lot of details. I’ve certainly identified a couple of areas to follow up on, such as balanced translocation and nondisjunction, while I haven’t even mentioned partial translocation (which I don’t understand at all). I’ll come back to these another day as I’ve exceeded my hour already.

For a more detailed look at the genetics of Down’s syndrome try this article from the Down’s Syndrome Association, which was my main source of information. I’ll link to further articles later.

…with trisomy 21. I keep forgetting to note that while we are still waiting for G’s karyotype to be sent to us from the Kennedy-Galton Centre our consultant neonatologist did recently get a verbal confirmation of regular trisomy 21, as opposed to translocation or mosaic Down’s syndrome.

Which reminds me that I never did get around to writing that post on the genetics of Down’s syndrome. Stand by for that.

Stem cell research is a pretty controversial issue for some people. It’s not something I’ve spent too much time thinking about but as I have previously reported, it could potentially lead to improved understanding of, and treatment for, the effects of Down’s syndrome.

It is in that context that I think this Q&A in the New York Times is worth a read. It is an interview with Renee A. Reijo Pera, director of Stanford’s Center for Human Embryonic Stem Cell Research and Education.

While it is focused on the use of stem cells for fertility treatment it also helped me to understand some of the basic issues related to stem cell research.

Last night I fed my little boy his milk for the first time (also his first time on the bottle). This has to be one of the best moments in fatherhood in my opinion.

What made it even better was that while I was distracted trying to feed myself at the same time G – as I’m going to call him on here from now on – put both hands on the bottle and pushed it towards his mouth.

Our portage representative had said he should be putting one hand on the bottle pretty quickly but we should expect it to take a month or so before he was attempting to use both hands.

G was straight in there however. Earlier in the evening he was trying to hold some toy keys with both hands as well, although the bottle was a lot easier. I couldn’t be more proud.

I was going to save this until the New Year but it looks so much better than the old theme I’m going to activate it now. Credit to “colm.mcmullan” on Flickr for the picture, which is of a depiction of chromosomes at the London science museum. (N.B> I’m not using this image anymore but I may go back to it, so I’ll leave the link as a reminder).

The Telegraph, among others, reported last week that the UK Department of Health is resisting an order by the Information Commissioner to release data on abortions performed beyond 24 weeks on the grounds of disability.

According to the report, the DoH is resisting on the grounds that revealing the figures could lead to the identification of individuals – both patients and doctors – involved.

The Telegraph states:

“Health chiefs stopped publishing full abortion data three years ago after a public outcry over the termination of a foetus with a cleft palate at 28 weeks’ gestation. The legality of this late abortion, carried out in 2001, was challenged by a Church of England curate, Joanna Jepson, who was born with a congenital jaw defect.

In 2005 the Crown Prosecution Service decided not to bring any charges against the NHS consultant, who publicly confirmed that he carried out the procedure, and another doctor.

Ministers were sufficiently worried by the prospect of further complaints – which they argued would invade the privacy of doctors carrying out terminations and women having abortions – to strictly limit the publication of the figures.

From 2005, official abortion statistics were “suppressed” if fewer than 10 cases were carried out. This in effect meant that abortion details on babies with club feet, webbed fingers and toes, or cleft lips and palates, disappeared from public view.

The last year for which data were fully available, 2002, showed that five foetuses were aborted because they had deformed feet, and a sixth because of a cleft lip and palate. In 2000 and 2001, nine foetuses were aborted because of cleft lip and palate, while a further two were aborted for cleft lip alone.”

Information about the number of late abortions carried out on the grounds of disability was apparently requested by the Pro-Life Alliance using the Freedom of Information Act.

The DoH’s appeal against the commissioner’s decision (PDF) will now be heard by the Information Tribunal.

Congratulations are due to DownsEd and the Sue Buckley Research Fund which has raised almost £1m of new funds for practical research and dissemination since it was formed a year ago.

The Sue Buckley Research Fund is focused on “improving education for people with Down syndrome by accelerating progress in scientific research and ensuring widespread access to evidence-based advice and information.”

You can read all about the funds successes in 2008 and its plans for 2009 here, while you can read more about Sue and her story here.

Having read both yesterday I feel very humble and grateful that people like Sue and her son Frank and all the DownsEd staff have dedicated their lives to improving those of people with Down’s syndrome.

Here’s a short video about the work DownsEd does.

Angela Blakston has written an excellent column in The Age responding to recent calls for Australia to develop a national screening programme for Down’s syndrome (which I mentioned here).

Blakston is the mother to Gabriel, a 16-month old boy with Down’s syndrome, and makes a coherent argument for any increase in testing to be accompanied by information that provides both positive and negative perspectives.

She writes:

“For a choice to be truly informed, it must provide the full picture, the negatives and positives. While no medical professional ever openly questioned or disparaged our decision, any positive information, particularly early on, was generally conspicuously lacking.

This is the common experience of other women I’ve since met who knew they were carrying babies with Down syndrome.

It’s easy to lay blame with the medical profession. That’s not my intention. While I do believe it’s the job of medical professionals working in prenatal diagnostics to be properly informed on advances for people with Down syndrome and other genetic conditions. I also feel that much of the diagnostic and scanning technology (throughout all stages of pregnancy) is in such a nascent state that the medical profession, and society in general, has not properly worked through the ethical and moral dilemmas it throws up.”

She adds:

“I often ponder the irony that while prenatal scanning becomes more sophisticated and endemic, there has never been a better time than the present for a baby with Down syndrome to be born. There are the heart and other operations and medications available to ensure a high quality of life. There is the realisation of the crucial role of early intervention, with various physical and cognitive therapies for children. It is no coincidence that many children with Down syndrome are being integrated into and graduating from mainstream schools and beyond.

This is a large side to the story that is rarely told to expectant parents. My hope would be that any policy developed for uniform scanning would aim to keep abreast of advances in Down syndrome and clearly communicate these changes to expectant parents.”

I couldn’t agree more.

I was previously critical of Toys-R-Us’s “Toy Guide for Differently-abled Kids”, arguing that it was simply a list of toys with no real guidance on matching the abilities or disabilities of the child.

This list of tips to consider when choosing a toy for a child with special needs from the Kennedy Krieger Institute is much more useful.

It doesn’t really apply to us yet but someone out there may find it useful right now and I thought I’d post it here for future reference as well.

1) Buy toys that are developmentally appropriate, or match the child’s motor and cognitive skill level. If you don’t know where the child is developmentally, don’t be afraid to ask their parent.

2) Balance the child’s developmental age with their calendar age. Avoid hurt feelings and embarrassment by finding toys that are developmentally appropriate but not age-specific.

3) Choose toys that are engaging and help build skills. Simple, inexpensive toys such as balls, finger paints, blocks and play dough can build motor skills and coordination. Board games or toys that involve the whole family help build social skills.

4) Make sure the toy is durable and doesn’t have a lot of small pieces. Small pieces or easily broken toys can be a safety hazard, and some disabilities can make working with small pieces difficult.

5) Avoid toys that put kids in a “win or lose” situation. Pick toys and games that can build the child’s self-esteem, and that you know they can succeed in.