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

Abstract

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.

A rare de novo duplication of chromosome 21q22.12 → q22.3 with other concomitant deletion and duplication of small fragments in 21q associated with Down syndrome: Prenatal diagnosis, molecular cytogenetic characterization

“…To date, at least 39 cases of Down syndrome with pure partial tirsomy 21 have been reported [24,25], but the prenatal diagnosis of pure partial trisomy 21q associated with Down syndrome is quite rare. Lee et al, [26] reported a case of prenatal diagnosis of pure trisomy 21q(21q13 → q22.2) due to an unbalanced cryptic insertion (4;21)(q21;q22.1q22.3) inherited from the carrier father.…”

Gender Affects Clinical Suspicion of Down Syndrome

“…As an explanation for absence of trisomy 21 in different tissues of patients with apparent manifestations of the syndrome, several suggestions were proposed: (1) low-level mosaicism, (2) the presence of the trisomic cell line in tissues other than those investigated, (3) elimination of the aberrant cell line in vivo or selective regress in vitro [Engel et al, 1970], and (4) gene mutation that might cause a "phenocopy" [Hall, 1962]. Subsequent studies showed the presence of a cryptic duplication of the Down syndrome critical region in individuals with clinical diagnosis of Down syndrome and an apparently normal karyotype [see for reference Forster-Gibson et al, 2001]. However several patients with mental retardation and Down syndrome phenotype, but without molecularly detectable duplication of the critical region, have been reported [McCormick et al, 1989;Ahlbom et al, 1996].…”

Rapid Detection of Aneuploidy (Trisomy 21) by Allele Quantification Combined with Melting Curves Analysis of Single-Nucleotide Polymorphism Loci

“…In comparison with STRs, SNPs are more numerous and can better define the DSCR. Analysis of STRs in the DSCR should also detect partial trisomies (6 ), but to our knowledge, examples have not been reported, and discovery of partial duplication in chromosome 21 relies essentially on FISH technology (20 ). SNPs are the most abundant polymorphisms in the human genome with one SNP occurring each kilobase on average (13 ).…”