Multiple Chromosomal Aberrations in a Patient with Acute Granulocytic Leukemia Associated with Down's Syndrome and Twinning. Study of a Family with a Possible Tendency to Nondisjunction.

I N 1930, Brewster and Cannon’#{176} reported the first example of acute leukemia in a case of mongolism ( Down’s syndrome ) . Between 1947 and 1963, further reports appeared demonstrating the increased incidence of acute leukemia in Down’s syndrome.7”’#{176}”5’48’49’6#{176}’65’M7’#{176}’ In 1958, Stewart et al.TM5 reported that of 677 children dying of leukemia, 18 were associated with Down’s syndrome (2.6 per cent or nearly 20 times the incidence of leukemia in normals). By 1961, Stewart83 had found a total of 50 cases of Down’s syndrome associated with leukemia. It was not until 1956, that Tjio and Levan88 and Ford and Hamerton2’ conclusively established the normal number of human chromosomes as 46. A few years later, Lejeune, Turpin and Gautier 5 described the now classical G 21 trisomy in Down’s syndrome, the first example of a constant human chromosomal aberration associated with a specific disease. In 1960, a specific chromosomal anomaly, in association with chronic granulocytic leukemia (Philadelphia chromosome), was described.4m As a result, investigations of possible chromosomal aberrations in human neoplastic diseases were further stimulated. In some studies,76”7’90’#{176}4 no additional chromosomal anomalies were found in cases of leukemia occurring in Down’s syndrome, as compared with the non-leukemic cases. However, in other studies,’#{176}’54’73’93’95’#{176}8 a variety of chromosomal anomalies was found in cases of acute leukemia and mongolism, in addition to the chromosomal complement of classical Down’s syndrome. Eggen22 and McKusick57 in recent articles discussed chromosomal aberrations in Down’s syndrome as well as in other conditions. Recently, we had the opportunity of studying a 4-year-old boy with Down’s syndrome and acute granulocytic leukemia; a twin sister was normal. Numerous chromosomal aberrations in this patient, some of them never previously described; the occurrence of two sets of twins (with one affected twin in each set) in the family; and the presence of chromosomal aberra-