by Linda Cooper, M.S. and Jill C. Hennessey, M.S.

Down syndrome is a relatively common genetic condition estimated to occur once in every 600 to 700 live births in children of all races and ethnic backgrounds. Down syndrome is just one example of a birth-related disorder caused by a chromosome abnormality. Chromosomes are the rod-like structures present in all the cells of the body which carry the messages or genes that guide the development of a fetus. Human beings usually have 46 chromosomes, packaged as 23 pairs. Half of the chromosomes are received from the mother's egg and half from the father's sperm. Because there are thousands of genes present on the chromosomes, having too many or too few chromosomes causes problems for the developing fetus. Down syndrome is specifically caused by the presence of an extra copy of chromosome #21.

Although Down syndrome is considered a genetic disorder, it is usually not inherited. In the majority (90 to 95%) of individuals with Down syndrome, the extra #21 chromosome is separate and unattached and brings the total number of chromosomes to 47. This pattern is called trisomy 21. The extra chromosome is the result of an error in cell division of the egg or the sperm. The unequal distribution of chromosomes usually occurs prior to conception and is unrelated to environmental exposure or family history (Hook, 1982; Thuline & Pueschel, 1982).

Two to four percent of cases of Down syndrome are the result of the extra chromosome #21 being attached, or translocated, to another chromosome. In this situation, parental chromosomes are studied to determine whether either parent has a rearrangement involving a chromosome #21 (Mikkelsen, 1977).

The remaining 2% to 4% of Down syndrome cases are the result of mosaicism, a condition in which some of the cells of an individual have the normal 46 chromosomes and some have 47, with the extra being #21. This error in cell division may occur before or after conception, but, again, it is a random event and unrelated to outside influences. The chromosomal pattern of an individual with Down syndrome is not a predictor of mental functioning or physical characteristics. It is generally thought, however, that children with mosaic trisomy 21 may be more mildly affected.

The recurrence risk for a couple who has a child with Down syndrome depends on the child's specific chromosome status. Parents of a child with trisomy 21 are given a 1% risk for recurrence until the mother is about 36 years old, up to which time her risk is similar to that of the general population. This risk will continue to increase as she gets older. Paternal age does not seem to influence the occurrence of Trisomy 21. The risk for recurrence in couples when one parent carries a balance translocation depends on which parent carries the rearrangement and which two chromosomes are joined. Studies suggest the highest risk would be approximately 8% to 10%, if the mother is a carrier. Families who have a child with mosaic trisomy 21 may be at an increased risk over the general population for a recurrence.

Once a couple has had a child with Down syndrome, prenatal diagnosis is available to rule out chromosomal abnormalities in subsequent pregnancies. Chorionic villus sampling (CVS) is a procedure—done at around 10 weeks of gestation—whereby some fetal cells are obtained from the developing placenta for chromosomal analysis. The procedure is done either vaginally or transabdominally and has approximately a 0.5% (1/200) to 1% (1 in 1000) risk for miscarriage. Amniocentesis is an alternative procedure performed at 16 to 18 weeks gestation by withdrawing a small amount of fluid containing fetal cells from the amniotic sac. The risk of miscarriage for this procedure is approximately 0.33% (1 in 300). Although prenatal diagnosis can identify a fetus with Down syndrome or any other chromosomal abnormality, it cannot predict the mildness or severity of the condition.

Genetic counseling is available for families who have specific questions regarding recurrence risks and options for testing. All couples are at a 3% to 5% risk for having a child with a birth defect, most of which cannot be ruled out by prenatal testing. Couples who have had a child with Down syndrome are not at greater risk of having children with other types of birth defects. Testing during pregnancy is optional, and families can decide for themselves whether or not they want prenatal studies. The majority of families who opt for testing are reassured that their next child will not have a chromosomal abnormality.

References

Hook, E.G. (1982). Epidemiology of Down syndrome. In S.M. Pueschel & J.E. Rynders (Eds.), Down syndrome: Advances in biomedicine and behavioral sciences (p. 11). Cambridge, MA: Ware.

Mikkelsen M. (1977). Down syndrome: Cytogenetic epidemiology. Hereditas 86, (p. 45-59) Thuline, H.C. & Pueschel, S.M. (1982). Cytogenetics in Down syndrome. In S.M. Pueschel & J.E. Rynders (Eds.), Down syndrome, Advances in biomedicine and behavioral sciences (p. 133). Cambridge, MA: Ware.

The article above is reproduced from the Down Syndrome Guide disseminated by the Down Syndrome Clinic at Kennedy Krieger Institute. In accordance with federal copyright restrictions, the contents of this booklet may not be reproduced by photocopying or any other means without written permission from the copyright holder. © 1999 George Capone, M.D.


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