A family with multiple chromosome anomalies

Abstract

An 18 month male child, JM, was referred to Genetics because of developmental delay and coarse facial features. Chromosome analysis showed a mosaic male karyotype with an unidentified supernumerary ring chromosome in 12% of blood and 27% of skin cells and a normal male karyotype in the remainder. JM's father and uncle were found to be carriers for a balanced translocation inherited from their mother: 46, XY, t(6;22) (p24.1;q12.2)mat. The uncle has a deceased child with 45, X Turner syndrome. The t(6;22) predisposes to 3:1 segregation which may result in liveborn unbalanced offspring with a supernumerary der(22) trisomic for portions of 6p and 22q. FISH analyses of the supernumerary ring in JM were negative with wcp6 and wcp2 but positive with wcpB, identifying the ring as a pericentromeric derivative of chromosome 8: 47, XY, +r[12]/46, XY[88].ish r(8) (wcp8+). The clinical phenotype in JM is difficult to reconcile with the low percentage of abnormal cells and suggests a significantly higher proportion of partial trisomy 8 cells within the CNS. The presence of three apparently separate chromosome anomalies in this family may reflect either unfortunate coincidence or an undetermined familial predisposition to chromosome rearrangement and aneuploidy.