Down syndrome due to unbalanced homologous acrocentric rearrangements and its recurrence in subsequent pregnancies: prenatal diagnosis by amniocentesis.

OBJECTIVE To present our experience of amniocentesis for the prenatal diagnosis of Down syndrome due to unbalanced homologous acrocentric rearrangements and its recurrence in subsequent pregnancies. CASE REPORT From January 1987 to September 2009, six cases with rea(21q21q) Down syndrome were diagnosed among 31,194 patients who underwent amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. Cytogenetic analysis of parental blood lymphocytes was performed in each case, and polymorphic DNA markers were used to investigate the nature of the aberrant chromosome. Three of the six cases were associated with recurrence in subsequent pregnancies. The rea(21q21q) Down syndrome was associated with advanced maternal age in three cases, a previous child with rea(21q21q) Down syndrome in three cases, an abnormal maternal serum screening result in one case, and an abnormal ultrasound finding in one case. All six cases arose de novo. Among the six cases with molecular analysis results, all had isochromosome 21, five of which were determined to be of maternal origin. CONCLUSION We found a frequency of 0.019% for rea(21q21q) Down syndrome in patients undergoing amniocentesis. Down syndrome caused by the homologous rearrangement rea(21q21q) can be associated with recurrence. Prenatal diagnosis of rea(21q21q) Down syndrome should include extensive cytogenetic and molecular analyses of the parents and probands.