© 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.