Definition of "Down syndrome"

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Down syndrome is a genetic disorder caused by a 3rd copy of genes on chromosome 21.

Pathophysiology
  • Caused by 3 copies of the genes on chromosome 21, rather than the usual 2. This is caused by:
    • Trisomy 21 (most common cause, 93% of cases), is a complete extra copy of chromosome 21, caused by a failure of the 21st chromosome to separate during egg/sperm development. As the sperm/egg cell has an extra copy of chromosome 21, the cell has 24 [instead of 23] chromosomes. Thus, when combined, the baby has 47 [rather than 46] chromosomes, with 3 copies of chromosome 21. 88% of cases is due to nonseparation of the chromosomes in the mother, 8% from nonseparation in the father, and 3% after the egg and sperm have merged
    • Mosaic Down syndrome (1.7%), where some cells in the body are normal and others have trisomy 21
    • Translocations (2.5%), which contain additional material from chromosome 21. It may be a new mutation, or previously present in one of the parents (aka familial Down syndrome)

Patient information

What exactly is Down syndrome, and why does it happen?
It's where a baby receives 3 copies, rather than 2 copies of chromosome 21, a particular segment of code. It happens because rather than receiving 1 copy from mom, or 1 copy from dad, 2 copies are received instead.

Risk factors
  • Increasing maternal age, with 1 in 1,500 chance at 20yo, 1 in 1,000 chance at 30yo, 1 in 350 at 35yo, 1 in 100 chance at 40yo, and 1 in 30 chance at 45yo
  • 70% of kids with Down syndrome are born to women <=35yo, because younger people have more kids
  • Increasing paternal age is a risk factor in women older than 35yo, but NOT in women <35yo

Patient information

What determines whether my baby will have Down syndrome or not?
It's hard to say. But what we do know is that risk increases with age, especially the age of mom. As the age of the mother increases, the chance of Down syndrome happening increases. It starts at 1 in 1,500 at 20yo. By 30 yo it's 1 in 1,000. By 40yo it's 1 in 100. For younger women, the age of the dad doesn't matter as much. But older dad's are also a risk factor if the woman is older too.

Sx

Prevalence of Sx shown in brackets (in percentage%):

  • Neurological:
    • Mild to moderate intellectual disability (99%), with the average IQ as an adult Pt is 50 (i.e. mental age of 8-9yo), but this varies widely
    • Mental illness (30%), including autism (7%)
  • Physical:
    • Growth delays, reaching developmental milestones at a later age, and by adulthood, stunted growth (90%)
    • Morphological features:
      • Increased skin back of neck (80%)
      • Hypotonia (80%)
      • Narrow roof of mouth (76%)
      • Flat head (75%)
      • Flexible ligaments (75%)
      • Proportionally large tongue (75%)
      • Abnoraml outer ears (70%)
      • Flattened nose (68%)
      • Separation of first and second tose (68%)
      • Abnormal teeth (60%)
      • Slanted eyes (60%)
      • Shortened hands (60%)
      • Short neck (60%)
      • Bent 5th finger tip (57%)
      • Brushfield spots in the iris (56%)
      • Sngle transverse palmar crease (53%)
      • Protruding tongue (47%)
      • OSA (60%) → due to changes in airways
  • Senses, with hearing and vision disorders occurring in more than 50% of Pt's
    • Strasbismus (35%)
  • Heart:
    • Congenital heart disease (40%)
  • Cancer:
    • Leukemia
  • Endocrine:
  • GI:
    • Umbilical hernia (90%)
  • Fertility:
    • Undescended testicles (20%)

Patient information

What does a person with Down syndrome look like?
Because Down syndrome affects the code for 1 of the chromosomes of the 23 found in the body, there's a lot of things that can be affected. Essentially anything coded by that chromosome. What exactly happens depends on the lottery of life. But there are some things that are more likely to occur than others, and this ranges anywhere from not receiving a particular defect, to as being as sure as 99% for intellectual disability. But in short, there's brain related things. So apart from intellect, there's also mental illness, and autism. There's a number of physical features, increased skin on the back of the neck, weaker strength, flat head, large tongue, growth delay. It can also affect the senses, heart, the intestines, really anything and everything in the body.

Dx
  • Screening, done prenatally, provided to all pregnant women regardless of age, better in both 1st (10-14 weeks) and 2nd trimester (15-18 weeks for the triple screen, 18-20 weeks for the 2nd U/S):
    • U/S, where during the 1st (10-14 weeks) and 2nd trimester (18-20 weeks) there is a small or no nasal bone, large ventricles, nuchal fold thickness, or an abnormal right subclavian artery. Increased fetal nuchal translucency [test] (NT scan, or NTT) indicates an increased risk of Down's, being sensitive for 77% of cases, and only having false positives in 6%
    • Maternal blood test (aka maternal serum screeningMSS), which detect 65% of cases, including:
      • Triple screen (aka Kettering test, or Bart's test), performed during the 2nd trimester (15-18 weeks) to classify a Pt as low or high risk for chromosomal abnormalities and neural tube defects. It includes:
        • Free beta-hCG
        • AFP (alpha-fetoprotein)
        • Unconjugated estriol
      • PAPP-A (pregnancy-associated plasma protein A) (see page)
  • Confirm Dx, if the triple screen shows greater than a cut-off point of 1 in 250 (probabilities as risky as 1 in 150 are used worldwide). 1 in 30 women identify as screen positive, but most will get a normal result on diagnostic testing. These tests are reserved for high risk, because they are invasive techniques, and include either:
    • Amniocentesis → 0.5% risk of miscarriage, usually done at 15-17 weeks
    • Chorionic villous sampling → 1% risk of miscarriage, usually done between 10-12 weeks
  • Observed after birth by direct observation
  • Genetic testing

Source: 2007/pdf/PD2007_067.pdf">NSW Health

Patient information

Abortion... is of course controversial . But even though a lot of women say they'd "keep the baby", when the wheels hit the road, even though 72% originally say they wouldn't, 93% eventually do. So, how do mothers find out whether their baby is going to have Down syndrome?
It starts with a screen. We do screens because they don't have the higher risk of miscarriage, like diagnostic tests do. So the way we do this is an ultrasound scan, measuring for the presence of certain features that make Down syndrome more likely. The thickness of the skin behind the neck, and other things like it. But that's not just all we do, because there can be a number of reasons why we might see these features. So we do it alongside 3 blood tests, what we call a triple screen. And from all these screens that we've done, we come up with a likelihood score. If that score is greater than 1 in 250 likelihood, we go on to the more invasive testing to confirm whether the baby actually has Down syndrome.

My screen came back positive The chance of my child having Down syndrome is greater than 1 in 250. I spent all day last night crying :'(
Don't be worried. 1 in 30 women screen as positive. But most will get a normal result on diagnostic testing. To give you an example of risk, by just age alone, by being 40yo, the risk of Down syndrome is 1 in 100. So where do we go from here? We confirm the diagnosis. We do this using 1 of 2 tests. We didn't do these tests earlier because they are invasive and have a chance for miscarriage, but because the risks are now higher, the benefits now outweigh the risks. We can do the amniocentesis which has a 0.5% risk of miscarriage, which has to be done later, after 15 weeks - or we can do the CVS which has a 1% risk of miscarriage, but can be done as early as 10 weeks.

What should I expect, and how long does the test take to do?
The test can be done using a needle through the abdomen, or through the cervix. The procedure through the abdomen should take less than 1 minute, or through the cervix should take no more than a couple of minutes. Both are just as safe as each other, but whereas through the abdomen causes a heavy pressure in the abdomen; through the cervix may cause discomfort similar to a papsmear, and some bleeding.

How long will it take for results to come back?
The diagnostic tests usually take 10-14 days. Some specialist centers may offer a rapid FISH test which can provide a result within 24 hours.

Ix
  • Regular screening for health problems common in Down's, throughout life, including:
    • ECG → heart problems
    • Heart U/S → heart problems
Tx
  • Prevention, by abortion, which occurs commonly following Dx
  • Early childhood intervention, including:
    • Speech therapy, or sign language
    • Inclusive education
  • Tx of common illnesses, including:
    • Surgical repair → heart problems
    • Hearing aids → hearing
    • Tonsillectomy → OSA, throat infections
    • Plastic surgery → appearance, improve speech
  • Good family environment
  • Work-related training

Patient information

If my fetus has been diagnosed with Down syndrome, what can I do about it?
Abortion is the most common thing mom's will decide. But even if you decide not to, there's a number of things that we can do. Relating to intellect, we can do early intervention, with speech therapy, and inclusive education. We can refer to Down syndrome support services, help initiate a good family environment. We can treat common things that happen in Down syndrome. Surgery for heart problems. Hearing aids for hearing. Tonsillectomy for sleep problems. Plastic surgery to improve speech or even appearance.

Prognosis
  • Life expectancy has increased from 12yo in 1912, to 50-60yo in the developed world in the 2000's
  • 8% will die in their first year of life
  • Higher risk of early death than general population, most often due to heart problems or infections (especially GI)
  • Long term survival is strongly determined by the presence of heart problems
  • Some Pt's with Down's graduate from high school, and a few attend University
  • 20% do paid work in some capacity in the USA, but only 1% have regular jobs in Europe
  • Support in financial and legal matters is often needed
  • Parents of affected individuals are typically normal
  • Parents with 1 child affected with Down syndrome, have a 1% of a 2nd child with Down's, if both parents have normal karyotypes
Epidemiology
  • It is the most common chromosome abnormality in humans, occurring in 1 in 1000
  • In 1986, 0.6% of babies were born with Down's, which is now down to 0.2% in 2004 → abortion
  • 95% of women opt for an abortion when they find out their baby has Down's
  • 67% of pregnancies in USA w/ pregnancy are terminated, 92% are terminated in Europe
  • Whilst only 28% of non-pregnant people said they would abort following a positive test, 66% of high risk women said they would. 93% of those who screen positive eventually opt for an abortion
See also
  • Nuchal scan (Ix)

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Definition of Down syndrome | Autoprac


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