Tetraploid-Diploid Mosaicism in a Surviving Infant

Extract: Although tetraploidy and tetraploid-diploid mosaicism has been well documented in studies of aborted human fetuses, no living case has been reported. This report concerns a male infant with tetraploid-diploid mosaicism who survived for 36 weeks. Because the peripheral blood cells of this infant displayed gross differences both in cell size and in DNA content, it was possible to establish that the tetraploidy observed in cultured cells was a true reflection of in vivo mosaicism. The propositus was born on December 6, 1965, after a 42-week gestation notable for a paucity of fetal movement. Birth weight was 1.7 kg, length 40.6 cm and head circumference 25.4 cm. He presented with multiple congenital anomalies. Peripheral blood smears appeared to contain two populations of neutrophilic granulocytes that differed in overall size. Immunological assessment gave the following results : 1. Serum immunoelectrophoresis performed at the ages of 4, 10 and 14 weeks showed qualitatively normal immunoglobulins. 2. Normal antibody responses were obtained to type I polio and to typhoid-paratyphoid vaccines given at age 10 weeks. 3. Normal delayed hypersensitivity was obtained following stimulation with 2,4-dinitrofluorobenzene at the age of 12 weeks. There was a normal plasma growth hormone response to insulin-induced hypoglycemia at 12 weeks of age. Many of the cells in follicular centers of the spleen and lymph nodes were pale, and the lymphocytes surrounding them were bizarre, being unusually large and hyperchromatic. The histologic architecture was preserved and cortico-medullary differentiation maintained. Tetraploid-diploid mosaicism was found in ten short-term cultures of peripheral blood leukocytes obtained over a seven-month period. The average proportion of tetraploid cells was 69 % (range 64 to 77 %). Chromosomal analysis of six different primary fibroblast cultures, including that derived from the postmortem lung, were diploid in number and euploid in karyotype. Peripheral blood smears appeared to have two populations of neutrophilic granulocytes which differed from one another in their overall size. The distributions of cell diameters from all of the subject's smears showed highly significant positive skewing, in contrast to the more symmetrical distributions from the control smears. Analysis of bimodality, using a computer, indicated the presence of two normally distributed subpopulations. The results generated are given in table IV. Cytophotometric measurements of cellular DNA content can be used to analyze tetraploid-diploid mosaicism, since tetraploid cells have twice as much DNA as diploid cells. The large cells in peripheral blood from the subject had 2.01 times the stain content of his normal appearing cells, and 1.91 times that of the control. In order to estimate the incidence of tetraploidy among the subject's leukocytes, measurements were made on randomly selected cells and gave the results shown in table V. In the infant reported here, tetraploid-diploid mosaicism was evident only in the hematopoietic and lymphatic cells. Fibroblast cultures from skin, muscle and lung tissue were diploid. Different cell types showed different proportions of tetraploid cells, but these proportions were maintained throughout life. No functional abnormality was found in these tissues. Speculation: The marked growth disorder and congenital malformations of the infant discussed in this report indicate that there must have been severe disturbances present in other tissues. Perhaps tetraploid cells also occurred in those other tissues during the early stages of embryogenesis, but these cells were relatively deficient in their ability to undergo embryogenic differentiation and were gradually eliminated. The remaining diploid cells may have then been unable to compensate for the defunct tetraploid cells, thus leading to defects of organ development and of subsequent growth.