© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Conditions caused by anomalies in chromosome number

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© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Fig. 2.2 ©Scion Publishing Ltd

A child with Down syndrome

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Fig. 2.3 ©Scion Publishing LtdPhoto. (c) courtesy of Dr Godfrey Wilson

Turner syndrome

(a) Puffy feet. (b) redundant skin at back of neck. (c) Histology of gonads: ovarian cortical strome devoid of germ cell elements.

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

47,XX,+?mar

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Three different patterns of chromosomes can cause Down syndrome

•1% have mosaicism with normal and trisomy 21 cell lines (andusually have much milder features because of the presence of thenormal cells); occurs postzygotically

Non-disjunction

Non-disjunction

•95% people have three separate copies of chromosome 21 - trisomy 21

•4% have the extra copy of chromosome 21 because of a Robertsonian translocation

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Two other important autosomal trisomies

• Edwards syndrome (trisomy 18)– 1 in 3000 births– multiple malformations (especially heart, kidneys)– clenched hands with overlapping fingers

• Patau syndrome (trisomy 13)– 1 in 5000 births– multiple malformations– affects midline structures particularly:

incomplete lobation of brain; cleft lip; congenital heart disease

Both syndromes have a very poor prognosis: majority of babies dying in first few weeks of life. If a baby survives (very unusual) there is severe mental retardation.

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Two important conditions caused by anomalies of sex chromosome number• Klinefelter syndrome

– 47,XXY– 1 in 1000 males– Infertility (atrophic testes do not produce sperm)– Poorly developed 2ndy sexual characteristics in some (lack of

testosterone)– Tall

• Turner syndrome– 45,X– 1 in 5000 females – 99% are lost spontaneously in pregnancy– Short stature– Primary amenorrhoea (ovaries involute before birth)– Congenital heart disease (coarctation of aorta) 20%

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.geneticseducation.nhs.uk

Numerical chromosome abnormalities

• Gain or loss of complete chromosomes

• Common cause is non-disjunction (Usually in germ cells at meiosis. Occasionally in somatic cells resulting in mosaicism.)

• Serious, often lethal consequences (particularly autosomal anomalies)

• Autosomal monosomies catastrophic

• Fewer serious effects from sex chromosome anomalies

© 2009 NHS National Genetics Education and Development Centre

Genetics and Genomics for Healthcarewww.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 some 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.