Recurrent trisomy 21 in a couple with a child presenting trisomy 21 mosaicism and maternal uniparental disomy for chromosome 21 in the euploid cell line

Recurrence of trisomy 21 was observed in a family in which both parents had a normal chromosome complement. Mosaic trisomy 21 was found in a blood kar yotype of the first child, ii second pregnancy ended in spontaneous abortio n, and a full trisomy 21 was found at prenatal diagnosis of the third pregn ancy of this same couple. Although recurrent trisomy 21 may be due to chanc e, the possibility of germline mosaicism for trisomy 21 in one of the paren ts has important implications for recurrence risk. Molecular analysis was t herefore undertaken in this family to determine the parental origin and the stage of nondisjunction of the extra chromosome 21 in both cases. Although a maternal origin of both instances of trisomy 21 was observed, the mosaic case showed homozygosity for all markers along the duplicated maternal chr omosome, Such a finding would normally suggest a postzygotic origin of the trisomy 21, However, the diploid cell line in this same case showed materna l uniparental disomy 21, implying that it was the result of a trisomic conc eption. We suggest that a somatic nondisjunction in the maternal germ cells is the most likely explanation for these findings. The apparent meiotic II stage of nondisjunction of the nonmosaic trisomy 21 fetus was consistent w ith maternal mosaicism, A review of the literature for recurrent trisomy 21 cases studied by molecular means, suggests that mosaicism in germ cells ma y account for more cases than is detected cytogenetically. These results al so show that DNA marker analysis does not provide a valuable tool for patie nt counseling in case of recurrent trisomy 21, (C) 2000 Wiley-Liss, Inc.