A brief review of cryptic duplications of 21q as an emerging cause of Down syndrome: practical considerations for accurate detection

We review five cryptic duplications of 21q in patients with Down syndrome (DS) that were inherited from parental balanced translocations. All cases were identified by fluorescence in situ hybridization (FISH) and/or DNA diagnosis because the phenotype was inconsistent with the initial cytogenetic studies. These rearrangements seem to escape detection without expanded testing and are probably more frequent than expected. For this reason we propose a series of steps combining objective clinical diagnostic criteria, FISH and DNA methods to achieve an accurate ascertainment.