1. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Down Syndrome This PowerPoint file contains a number of slides that may be useful for teaching of genetics concepts. You may use these slides and their contents for non-commercial educational purposes. This set of slides contains information on: Clinical features of Down Syndrome Karyotypes of Trisomy 21 Meiotic Non disjunction FISH images

2. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Fig. 2.2 ©Scion Publishing Ltd A child with Down syndrome

3. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Down syndrome 1 in 700 live births >60% spontaneously aborted 20% stillborn 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

4. © 2009 NHS National Genetics Education and Development CentreSupporting 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 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 4% have the extra copy of chromosome 21 because of a Robertsonian translocation

5. © 2009 NHS National Genetics Education and Development CentreSupporting 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.

6. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Trisomy 21: 47,XX,+21 three separate copies of chromosome 21

7. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Fig. 2.11 ©Scion Publishing Ltd Karyotype showing trisomy 21 (47,XX,+21)

8. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Fig. 4.15 ©Scion Publishing Ltd 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.

9. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk 47,XX,+21

10. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk

11. © 2009 NHS National Genetics Education and Development CentreSupporting 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

12. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Meiotic Non-disjunction (Trisomy 21: 75% meiosis 1) TrisomyMonosomy (lethal)

13. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk 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.

14. © 2009 NHS National Genetics Education and Development CentreSupporting Genetics Education for Health www.geneticseducation.nhs.uk Trisomy 21 amniocyte