Discordant prenatal diagnosis of trisomy 21 due to mosaic structural rearrangements of chromosome 21

Prenat Diagn. 2003 Jun;23(6):461-9. doi: 10.1002/pd.620.

Abstract

Objectives: Trisomy 21 mosaicism associated with a structural rearrangement of chromosome 21 is uncommon. We report on two prenatal diagnoses in which karyotypes showed mosaicism with an aberrant cell line, including a structural rearrangement of chromosome 21.

Methods: Both these cases were associated with increased nuchal translucency. Conventional and molecular cytogenetic analyses were performed on uncultured and cultured trophoblast and amniotic fluid cells.

Results: In Case 1, analysis of trophoblast cells revealed an abnormal karyotype of 47,XX,+mar.ish der(13/21)(D13Z1/D21Z1+)/46,XX. The amniocentesis showed a free non-mosaic trisomy 21. In Case 2, the trophoblast direct analysis showed a normal male karyotype whereas the long-term culture revealed a mosaicism for a dicentric long-arm isochromosome 21: 46,XY,idic(21)(p11)/45,XY,-21/46,XY. Amniocentesis showed an unbalanced non-mosaic karyotype 46,XY,idic(21)(p11) resulting therefore in trisomy for the long arm of chromosome 21.

Conclusion: Our cases underline the importance of combining the direct analysis and long-term culture of trophoblast and emphasise the need for confirmatory studies in other tissues when mosaicism of structural rearrangement is encountered in chorionic villi. The meiotic and mitotic mechanisms of formation of these structural rearrangements of chromosome 21 are discussed.

MeSH terms

  • Adult
  • Amniocentesis
  • Amniotic Fluid / cytology
  • Cells, Cultured
  • Chorionic Villi Sampling
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 21*
  • DNA / blood
  • Down Syndrome / diagnosis*
  • Female
  • Genetic Markers / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Male
  • Mosaicism*
  • Neck / diagnostic imaging
  • Neck / embryology
  • Polymerase Chain Reaction
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Reproducibility of Results
  • Ultrasonography

Substances

  • Genetic Markers
  • DNA