Welcome to Illinois

Getting it wrong and telling it right

Posted in Attitudes to disability, Campaigns, Personal, Screening by Matt at WelcometoIllinois on January 2, 2010

My older sister is currently expecting her second child. Being a few years older, and therefore statistically more likely to have a child with Down’s syndrome, and also having seen from our experience that it pays to be prepared, she is likely to have a combined test in the coming weeks to assess the possibility that my new niece or nephew has DS.

However, this post isn’t about my sister or the next addition to our family. Its about the health care “professional” who told my sister that she shouldn’t be overly concerned there is a history of Down’s syndrome in the family since the link is via her brother (me) and Down’s syndrome “is passed down the mother’s side”.

The ignorance revealed in that statement is staggering. To be clear, Down’s syndrome can be the result of inheritance from one of the parents (who would not show any signs of chromosomal abnormality) but that form of translocation occurs in only 1/3 of 4% of cases of Down’s syndrome, and in any case can be inherited from either the father or the mother.

This information itself would only be relevant in my sister’s case if G had Translocation Down’s syndrome, which he doesn’t. But then it sounds like the health care worker concerned is having trouble with the basics, let alone the difference between Trisomy 21, Translocation and Mosaic Down’s syndrome.

It is frightening to think that someone lacking a basic understanding of Down’s syndrome is providing advice to expectant couples.

It is also a timely reminder that the Down’s Syndrome Association’s Tell it Right campaign involves a petition to the UK Prime Minister to provide high quality information in the diagnosis of Down’s syndrome. For those in the UK there are just five days left to sign the petition.

The genetics of Down’s syndrome in 60 minutes

Posted in Genetics, Statistics by Matt at WelcometoIllinois on December 19, 2008

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:

  • Regular trisomy 21
  • Translocation
  • Mosaic
  • 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.

    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.

    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.