Down Syndrome
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This set of slides contains information on:
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Clinical features of Down Syndrome
Karyotypes of Trisomy 21
Meiotic Non disjunction
FISH images
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
A child with Down syndrome
Fig. 2.2 ©Scion Publishing Ltd
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Down syndrome
• 1 in 700 live births
• >60% spontaneously aborted
• 20% stillborn
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Facial appearance permits diagnosis
Marked muscle hypotonia as baby
Single palmar crease may be present
Learning difficulty (IQ usually <50)
Congenital heart malformations (40%)
Many other associated features
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Three different patterns of chromosomes can cause Down syndrome
• 95% people have three separate copies of
chromosome 21 - trisomy 21
• 4% have the extra copy of chromosome 21 because
of a Robertsonian translocation
Non-disjunction
Non-disjunction
• 1% have mosaicism with normal and trisomy 21
cell lines (and usually have much milder features
because of the presence of the normal cells); occurs postzygotically
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Trisomies appear to be associated with an increase in maternal age
• eggs held at crossing-over stage in meiosis from approx 6 months gestation
• so ‘wear and tear’ with increasing maternal age in machinery for cell division
thought to be a major component (plus other factors)
The trisomy 21 type of Down syndrome is the result of an error in meiosis,
and has a recurrence risk of about 1 in 100.
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Trisomy 21: 47,XX,+21
three separate copies of chromosome 21
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Karyotype showing trisomy 21 (47,XX,+21)
Fig. 2.11 ©Scion Publishing Ltd
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Interphase FISH test for trisomy 21
The chromosome 21 probe is labelled with a red fluorochrome and a control probe (for chromosome 18) is
labelled in green. The two green dots show that the hybridization has worked for this cell, and the three red
dots show that there are three copies of chromosome 21. The clinical report is based on examining a large
number of cells. For prenatal diagnosis a mix of differently coloured probes from chromosomes 13, 18, 21,
X and Y is often used.
Fig. 4.15 ©Scion Publishing Ltd
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
47,XX,+21
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Non-disjunction in meiosis I resulting in trisomy 21 Down syndrome
Animation from Tokyo Medical University
Genetics Study Group Hironao NUMABE, M.D
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Meiotic
Non-disjunction
(Trisomy 21:
75% meiosis 1)
Trisomy
© 2009 NHS National Genetics Education and Development Centre
Monosomy (lethal)
Supporting Genetics Education for Health
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Incidence of trisomy 21 at the time of chorionic villus sampling (10-11 weeks), amniocentesis (16 weeks)
and term.
The incidence of trisomy 21 increases with increasing maternal age.
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Trisomy 21 amniocyte
© 2009 NHS National Genetics Education and Development Centre
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk