Skip to Main Content


Key Points

  • Ninety percent of individuals with Down syndrome have three full copies of chromosome 21. Three to 4% have an unbalanced translocation, and 1% have mosaicism.

  • Prevalence in the United States is 13.65 per 10,000 livebirths.

  • Fetuses with Down syndrome are more likely to die in utero than normal fetuses.

  • Karyotype analysis is diagnostic.

  • Once trisomy 21 is diagnosed, prospective parents should be offered an echocardiogram and a detailed sonographic evaluation of fetal anatomy (if not performed previously). Fifty percent of fetuses have cardiac anomalies.

  • If no structural heart disease or gastrointestinal obstruction is present, delivery can occur in the community. If structural anomalies in the heart or other organs are present, delivery should occur in a tertiary center.

  • Newborns often have feeding difficulties due to hypotonia.

  • There is an increased risk of hematologic disorders and hypothyroidism.

  • Affected children have mild to moderate mental retardation (IQ 40—70).

  • The precise number and function of genes of 21q is not fully known.

  • Recurrence risk for full trisomy 21 is 1%, or the maternal age-associated risk (whichever is greater).


Trisomy 21 is an abnormality due to the presence of an extra copy of chromosome 21 (Figure 131-1). Individuals with the clinical characteristics of what we now know as Down syndrome were first described by Dr. John Langdon Down in 1866. Dr. Down was a physician at the Earlswood asylum in Surrey, England. His erroneous ideas about a racial cause for Down syndrome, along with a superficial similarity in facial appearance to persons of mongoloid origin, led to the term mongolism (Cooley and Graham, 1991). Interestingly, Dr. Down eventually had a grandson who was also named John Langdon Down, and he had Down syndrome (Patterson and Costa, 2005).

Figure 131-1

Karyotype from a female individual with Down syndrome, indicating the presence of three copies of chromosome 21. (Courtesy of Dr. Janet Cowan.)

The association between the clinical entity Down syndrome and an extra copy of chromosome 21 was noted simultaneously in 1959 by Drs. Jerome Lejeune in France and Patricia Jacobs in Scotland. Ninety-five percent of individuals with Down syndrome have three copies of chromosome 21, which results from meiotic nondisjunction of the pair of number 21 chromosomes in the formation of an egg or sperm prior to fertilization (Sherman et al., 2005). Ninety-four percent of the time, the extra copy of the chromosome 21 is maternal in origin (Antonarakis, 1991). Approximately 3% to 4% of cases of Down syndrome are due to an unbalanced translocation involving chromosome 21. Fifty percent of the translocation cases occur spontaneously (de novo) and 50% are inherited from a parent with a balanced translocation. One percent of cases of Down syndrome are due to mosaicism, beginning as a trisomic conceptus with selective ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.