Abstract
This unique case with two supernumerary marker chromosomes of different origins demonstrates the value of using array comparative genome hybridization (array-CGH) with pericentric clones for the identification of marker chromosomes. A 27-month-old hypotonic male was found, by conventional cytogenetics, to be mosaic for a marker chromosome. Analysis of a blood specimen revealed 47,XY,+mar[31]/48,XY,+2mar[1]/46,XY[3]. Microarray CGH (SignatureChipTM) utilizing 230 genetic loci on 41 chromosome arms, including all pericentric regions, detected single copy gains at 11q12 and 17p11.2 pericentromeric regions. The area of gain on 17p did not include the Smith Magenis syndrome region. Fluorescence in situ hybridization using BAC clones from 11q12 (RP11-872D17+) and 17p11.2 (RP11-846F4+) identified two marker chromosomes: one marker of chromosome 11 origin in 4/11 cells, one marker of chromosome 17 origin in 3/11 cells and two markers, one of each chromosomal origin, in 4/11 cells. After a normal pregnancy and delivery, hypotonia and poor head control were apparent at 6 months. He responded well to physical therapy and walked at 23 months. He now imitates housework, helps with dressing, has a 30-word vocabulary, and uses 2-word phrases. There are no behavior or sleep problems. Growth is normal, but head circumference is at the 98th%ile. Physical exam shows a socially appropriate, playful toddler with dysmorphic features. There is dolicocephaly, prominent glabella, short upturned nose, long philtrum and thin upper lip, diastasis recti, tapered fingers, joint hypermobility, pes planus, hypotonia, and normal reflexes. Lab studies are normal, as are MRI of the brain and ophthalmologic examination. Among large published studies of supernumerary marker chromosomes, the finding of two markers from two different chromosomal origins is rare and, to our knowledge, no cases have been reported with two markers derived from chromosomes 11 and 17 in the same patient. We conclude that array-CGH is a powerful adjunct to cytogenetic investigations, and with pericentric clones, it is particularly useful in the identification of marker chromosomes. In this case, it not only identified the origin and size of the duplicated regions but also revealed a previously unsuspected level of complexity. The characterization of additional marker chromosomes by array-CGH will identify their chromosomal origins and the extent of euchromatin content and allow for phenotype-genotype correlations among similar cases.
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