Congenital marrow dysfunction in Down's syndrome

doi:10.1016/S0022-3476(70)80335-3

The Journal of Pediatrics

Volume 77, Issue 2, August 1970, Pages 273-279

https://doi.org/10.1016/S0022-3476(70)80335-3 Get rights and content

During an epidemiologic study of neonatal polycythemia, 9 infants with Down's syndrome were observed among 402 study cases. The number observed was 19.2 times greater than expected, a significant excess. An analysis of the demographic and clinical characteristics of these infants suggested no explanation for their polycythemia. Quantitatively and qualitatively, however, red cell proliferation in these infants appears analogous to granulocyte and platelet abnormalities previously reported. This finding supports previous suggestions of an extensive congenital defect of bone marrow function in newborn infants with Down's syndrome.

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Transient myeloproliferative disorder (transient leukemia) and hematologic manifestations of Down syndrome
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Transient Myeloproliferative Disorder (Transient Leukemia) is found in approximately 10% of newborn infants with Down Syndrome. It is characterized by the large numbers of megakaryo-blasts in the peripheral blood, variable thrombocytopenia and, in a minority of cases, by a lethal course with hydrops fetalis or progressive hepatic fibrosis. Evidence is presented that this disease is truly leukemia, which, in most cases, recovers spontaneously. There is evidence that hematopoiesis is abnormal in Down Syndrome children who do not have leukemia. These abnormalities of red cells, platelets, and granulocytes are reviewed.
Incidence, significance, and kinetic mechanism responsible for leukemoid reactions in patients in the neonatal intensive care unit: A prospective evaluation
1996, Journal of Pediatrics
OBJECTIVE: To prospectively investigate the incidence, significance, and kinetic mechanism responsible for leukemoid reactions in patients in the neonatal intensive care unit (NICU). DESIGN: We prospectively studied all infants admitted to the NICU at the University of Florida who, during a period of 12 consecutive months, had a leukemoid reaction. All those identified had a standardized evaluation consisting of (1) karyotype analysis, (2) bacterial cultures, (3) evaluations for toxoplasmosis, other (congenital syphilis and viruses), rubella, cytomegalovirus, and herpes simplex virus) (TORCH), (4) determination of blood viscosity, (5) use of marrow aspirates for morphology, clonogenic progenitor cell assays, and cell-cycle analysis of progenitors, (6) determination of serum concentrations of granulocyte and granulocyte-macrophage colony-stimulating factors, and (7) serial complete blood cell counts until the leukemoid reaction remitted. RESULTS: During 12 months, 707 patients were admitted to the NICU and 4262 complete blood cell counts were performed on samples from these patients. A leukemoid reaction was identified in nine patients, all of whom were preterm (born at 24 to 38 weeks' gestation). Peak blood leukocyte concentrations were 51.7 ± 15.6 × 10³/μl (mean ± SD). The leukemoid reactions were detected during the first 4 days of life in seven patients, on day 9 in one, and on day 25 in one. An abnormal karyotype (47,XY, +21) was present in one infant. Mothers of four infants had received betamethasone antenatally. None had elevated whole blood viscosity or positive findings on bacterial or TORCH evaluations. None of the bone marrow findings were consistent with steroid-induced leukocytosis; all studies indicated accelerated neutrophil production. Serum concentrations of granulocyte-macrophage colony-stimulating factor were either negligible or nondetectable. Serum granulocyte colony-stimulating factor was elevated in three patients, low in two, and nondetectable in four. The leukemoid reactions persisted for 5 to 32 days, the longest being in the patient with trisomy 21. CONCLUSIONS: Leukemoid reactions were not particularly rare in our NICU (1.3% of patients). The reactions were not associated with hyperviscosity and, except in one patient with a karyotype abnormality, were transient. The responsible kinetic mechanism was increased neutrophil production, not steroid-induced leukocytosis. (J PEDIATR 1996;129:403-9)
Amniotic fluid erythropoietin levels in normal and Down's syndrome pregnancies
1994, European Journal of Obstetrics and Gynecology and Reproductive Biology
The aim of this study was to measure the levels of erythropoietin in amniotic fluid from normal and trisomy 21 pregnancies at 10 to 20 weeks gestation. Samples of amniotic fluid were collected from 142 women with singleton pregnancies after genetic amniocentesis; 110 had a normal fetal karyotype and 32 had trisomy 21. Erythropoietin was measured using a double antibody radioimmunoassay. Amniotic fluid erythropoietin levels in normal pregnancies increased from 10 weeks (mean 3.2 mU/ml; range < 2.0–6.3 mU/ml) to 20 weeks gestation (mean 7.9 mU/ml; range 2.0–11.5 mU/ml). There was a significant linear correlation between gestational age and erythropoietin levels (r = 0.543; P < 0.0001). For the 32 patients with trisomy 21 pregnancies the median multiple of the median (MoM) was 1.11 (range 0.42–2.1). There was no difference between erythropoietin levels in amniotic fluid from normal and Down's syndrome pregnancies (U = 2352, P = 0.75, 95% CI = −0.11, 0.18); (Mann-Whitney U-test).
Down's syndrome and leukemia: Epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis
1987, Cancer Genetics and Cytogenetics
The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population. The age of onset for leukemia in these children is bimodal, peaking first in the newborn period and again at 3–6 years. This increased risk extends into adulthood.
All cytogenetic types of Down's syndrome apparently predispose to leukemia. The proportion of acute lymphoblastic leukemia and acute nonlymphoblastic leukemia in patients with Down's syndrome is similar to non-Down's syndrome leukemia patients matched for age. There are case reports in which leukemia, Down's syndrome, and other chromosomal aberrations cluster within a family. In these kindreds, there may be a familial tendency toward nondisjunction.
Congenital leukemia also occures with increased frequency in Down's syndrome patients, and is characterized by a preponderance of acute nonlymphoblastic leukemia (similar to non-Down's syndrome patients). Transient leukemoid reactions have been observed in Down's syndrome patients, as well as in phenotypically normal children with constitutional trisomy 21 mosaicism. The transient leukemoid reactions are characterized by a high spontaneous remission rate. However, in some Down's syndrome patients with apparent transient leukemoid reaction, leukemia relapse following periods of spontaneous remission have been reported.
Cytogenetic studies of leukemic cells in Down's syndrome patients show a tendency toward hyperdiploidy. Besides trisomy 21, there is no other specific cytogenetic abnormality that is characteristic of the leukemia cells in Down's syndrome patients. The possible mechanisms for leukemogenesis in Down's syndrome patients may involve factors at the levels of the organism, the organ/system, the cell, the chromosomes or the DNA.
Hematological changes in down's syndrome
1986, Critical Reviews in Oncology and Hematology
The many hematological abnormalities observed in patients with Down's syndrome have intrigued hematologists for many years. This review summarizes recent studies concerning the hematological findings in newborn infants with Down's syndrome; the transient leukemold/leukemia-like proliferative disorders in these infants; the increased incidence of leukemia and types of leukemia in patients with Down's syndrome; and immunological studies of these patients.
Neonatal polycythemia and hyperviscosity
1982, Pediatric Clinics of North America

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^*: Present address: Pediatric Department, National Jewish Hospital and Research Center, 3800 E. Colfax, Ave., Denver, Colorado 80206.

^**: Present address: Pediatric Department, Kaiser Permenente Clinic, 5055 N. Greeley Ave., Portland, Oregon 97217.

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Special articleCongenital marrow dysfunction in Down's syndrome

J. Pediat.

J. Pediat.

J. Pediat.

J. Pediat.

Amer. J. Dis. Child.

Amer. J. Dis. Child.

Probl. Gemat.

J. Nat. Cancer Inst.

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J. A. M. A.

The simultaneous occurrence of leukemia and mongolism

Arch. Dis. Child.

The structure and scope of the collaborative project on cerebral palsy, mental retardation, and other neurological and sensory disorders of infancy and childhood

An application of the U. S. Bureau of the Census socioeconomic index to a large, diversified population

Soc. Sci. Med.

Special article
Congenital marrow dysfunction in Down's syndrome