Cryptic duplication of 21q in an individual with a clinical diagnosis of Down syndrome.

We describe an adult male who was diagnosed with Down syndrome (DS) at 9 months of age, but had repeatedly normal karyotypes until recent mid-resolution chromosome studies showed a possible duplication of 21q22.13 to 21q22.3. The abnormality was investigated using fluorescent in situ hybridization (FISH) studies. These showed hybridization of a whole chromosome paint probe (wcp21, Oncor Coatasome 21) to the entire length of both chromosome 21 homologues and one very large hybridization signal of a cosmid contig probe localized within bands 21q22.13-21q22.2(LSI-21, Vysis) on the ?dup(21q) homologue. CGH analysis identified a ratio of 1.5 for the segment of chromosome 21 involving band 21q22, indicating a gain of part, or all, of the terminal band of chromosome 21. The karyotype was thus defined as 46,XY,?dup(21) (q22.13q22.2).ish dup(21)(LSI-21++,wcp21+). Common DS characteristics in our case and 12 previously reported cases with duplications involving chromosome 21 included mental retardation, fifth finger clinodactyly, open mouth and oblique eye fissures. Transverse palmar creases and congenital heart defects, seen in DS less than 40% of the time, were infrequent. Presence of these features did not appear to depend on the specific portion of chromosome 21 that was duplicated. A review of 18 additional clinical features showed no consistent phenotype-genotype correlations.