Trisomy 21 mosaicism in gonads with unexpectedly high recurrence risks

The recurrence risk for Down syndrome (DS) is about 1% in case of a previous offspring with trisomy 21 and minimal in case of a de novo (21;21) translocation. We have monitored 1,211 pregnancies in the first and second trimester after a prior occurrence of trisomy 21. Six couples had a trisomy 21 fetus in a subsequent pregnancy. We studied their lymphocytes, fibroblasts, and in one case ovaries, to detect parental mosaicism for chromosome 21. We detected mosaicism in 2 parents with 3 and 4 pregnancies, respectively, in which trisomy 21 was found. In one it was present in 47% of cells from the ovaries. Another couple with a pregnancy monitored because of a first child with a de novo (21;21) translocation had normal chromosomes themselves and one normal child, but 2 more pregnancies with a (21;21) translocation. It is concluded that thorough cytogenetic study of parents is indicated after 2 pregnancies with regular or translocation trisomy of chromosome 21. Genetic counseling should consider the possibility of an elevated recurrence risk due to gonadal mosaicism in one parent.