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 mo nths of age, but had repeatedly normal karyotypes until recent mid-resoluti on 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 hom ologues and one very large hybridization signal of a cosmid contig probe lo calized within bands 21q22.13-21q22.2(LSI-21,Vysis) on the ?dup(21q) homolo gue. CGH analysis identified a ratio of 1.5 for the segment of chromosome 2 1 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) (q2 2.13q22.2).ish dup(21)(LSI-21+ +,wcp21+). Common DS characteristics in our case and 12 previously reported cases with duplications involving chromosom e 21 included mental retardation, fifth ringer clinodactyly, open mouth and oblique eye fissures. Transverse palmar creases and congenital heart defec ts, seen in DS less than 40% of the time, were infrequent. Presence of thes e features did not appear to depend on the specific portion of chromosome 2 1 that was duplicated. A review of 18 additional clinical features showed n o consistent phenotype-genotype correlations.