Tertiary trisomy due to a reciprocal translocation of chromosomes 5 and 21in a four-generation family

Tertiary trisomy, or double trisomy, is a rare occurrence. We present two i ndividuals with a previously unreported tertiary trisomy for chromosomes 5p and 21q in an eight-generation pedigree. Their phenotypes are compared wit h other partial trisomies of either 5p or 21q from the literature. The prop ositus was diagnosed with trisomy 21 at 2 years of age after a karyotype st udy for short stature and developmental delay. His phenotype was described as atypical for Down syndrome. He presented at 9 years of age because of pe rvasive behavioral problems and obesity. He was brachycephalic with a flatt ened nasal bridge, but he lacked other characteristics of trisomy 21. Becau se of lack of phenotypic evidence of Down syndrome, a repeat karyotype was obtained and showed 47,XY,+der(21)t(5;21) (p15.1; q22.1), incorporating par tial trisomies of both chromosomes 5 and 21. Mother had a balanced transloc ation, 46,XX,t(5;21)(p15.1; q22.1); 8 other relatives were examined. The tr anslocation originated from the maternal great-grandmother, but only the pr opositus and his mentally retarded aunt had a similar phenotye and the deri vative chromosome. Fluorescence in situ hybridization showed absence of ban d 21q22.2 in the derivative chromosome of the propositus and his aunt, indi cating that neither had trisomy for the Down syndrome critical region. Thes e cases represent a unique double partial trisomy of chromosome arms 5p and 21q that occurred because of 3:1 malsegregation of a reciprocal translocat ion. These cases further demonstrate that phenotypic discordance with cytog enetic results dictate further investigation using advanced cytogenetic hyb ridization. Am. J. Med. Genet. 92:311-317, 2000. (C) 2000 Wiley-Liss, Inc.