Ring chromosome 15: phenotype, Ag-NOR analysis, secondary aneuploidy, and associated chromosome instability

Cytogenetic analysis of a 15 month old girl evaluated for severe developmental delay and acral skeletal hypoplasia revealed a predominant 46, XX, r(15) karyotype. Prophase banding analysis showed minimal deletion of the ring chromosome (breakpoints pl2 and q26), while silver staining showed it to have an active nucleolus organizing region, multiple abnormal secondary configurations, and decreased satellite association. Although there was no spontaneous instability in the rest of the karyotype, gentian violet-induced chromosome breakage was significantly increased. The rate of spontaneous sister chromatid exchange was not elevated. Cellular mosaicism for chromosome 15 aneuploidy most likely accounts for the patient’s phenotypic abnormalities.